Reconstitution and resonance assignments of yeast OST subunit Ost4 and its critical mutant Ost4V23D in liposomes by solid-state NMR.

N-linked glycosylation is an essential and highly conserved co- and post-translational protein modification in all domains of life. In humans, genetic defects in N-linked glycosylation pathways result in metabolic diseases collectively called Congenital Disorders of Glycosylation. In this modification reaction, a mannose rich oligosaccharide is transferred from a lipid-linked donor substrate to a specific asparagine side-chain within the -N-X-T/S- sequence (where X ≠ Proline) of the nascent protein. Oligosaccharyltransferase (OST), a multi-subunit membrane embedded enzyme catalyzes this glycosylation reaction in eukaryotes. In yeast, Ost4 is the smallest of nine subunits and bridges the interaction of the catalytic subunit, Stt3, with Ost3 (or its homolog, Ost6). Mutations of any C-terminal hydrophobic residues in Ost4 to a charged residue destabilizes the enzyme and negatively impacts its function. Specifically, the V23D mutation results in a temperature-sensitive phenotype in yeast. Here, we report the reconstitution of both purified recombinant Ost4 and Ost4V23D each in a POPC/POPE lipid bilayer and their resonance assignments using heteronuclear 2D and 3D solid-state NMR with magic-angle spinning. The chemical shifts of Ost4 changed significantly upon the V23D mutation, suggesting a dramatic change in its chemical environment.

Clinical trial recommendations using Semantics-Based inductive inference and knowledge graph embeddings.

OBJECTIVE: Designing a new clinical trial entails many decisions, such as defining a cohort and setting the study objectives to name a few, and therefore can benefit from recommendations based on exhaustive mining of past clinical trial records. This study proposes an approach based on knowledge graph embeddings and semantics-driven inductive inference for generating such recommendations. METHOD: The proposed recommendation methodology is based on neural embeddings trained on first-of-its-kind knowledge graph constructed from clinical trials data. The methodology includes design of a knowledge graph for clinical trial data, evaluation of various knowledge graph embedding techniques for it, application of a novel inductive inference method using these embeddings, and generation of recommendations for clinical trial design. The study uses freely available data from clinicaltrials.gov and related sources. RESULTS: The proposed approach for recommendations obtained relevance scores ranging from 70% to 83%. These scores were determined by evaluating the text similarity of recommended elements to actual elements used in clinical trials that are in progress. Furthermore, the most pertinent recommendations were consistently located towards the top of the list, indicating the effectiveness of our method. CONCLUSION: Our study suggests that inductive inference using node semantics is a viable approach for generating recommendations using graphs neural embeddings, and that there is a potential for improvement in training graph embeddings using node semantics.

Interlinkage Between Persistent Organic Pollutants and Plastic in the Waste Management System of India: An Overview.

Improper handling of plastic waste and related chemical pollution has garnered much attention in recent years owing to the associated detrimental impacts on human health and the environment. This article reports an overview of the main interlinkages between persistent organic pollutants (POPs) and plastic in the waste management system of India. Both plastics and POPs share certain common traits such as persistence, resistance to biological degradation, and the ability to get transported over long distances. Throughout the processes of production, consumption, and disposal, plastics interact with and accumulate POPs through several mechanisms and end up co-existing in the environment. Plastic waste can undergo long-range transport through rivers and the oceans, break down into microplastics and get transported through the air, or remain locked in waste dump yards and landfills. Over time, environmental processes lead to the leaching and release of accumulated POPs from these plastic wastes. Plastic recycling in the Indian informal sector including smelting, scrubbing, and shredding of plastic waste, is also a potential major POPs source that demands further investigation. The presence of POPs in plastic waste and their fate in the plastic recycling process have not yet been elucidated. By enhancing our understanding of these processes, this paper may aid policy decisions to combat the release of POPs from different waste types and processes in India.

NMR and MD simulations reveal the impact of the V23D mutation on the function of yeast oligosaccharyltransferase subunit Ost4.

Asparagine-linked glycosylation, also known as N-linked glycosylation, is an essential and highly conserved co- and post-translational protein modification in eukaryotes and some prokaryotes. In the central step of this reaction, a carbohydrate moiety is transferred from a lipid-linked donor to the side-chain of a consensus asparagine in a nascent protein as it is synthesized at the ribosome. Complete loss of oligosaccharyltransferase (OST) function is lethal in eukaryotes. This reaction is carried out by a membrane-associated multisubunit enzyme, OST, localized in the endoplasmic reticulum. The smallest subunit, Ost4, contains a single membrane-spanning helix that is critical for maintaining the stability and activity of OST. Mutation of any residue from Met18 to Ile24 of Ost4 destabilizes the enzyme complex, affecting its activity. Here, we report solution nuclear magnetic resonance structures and molecular dynamics (MD) simulations of Ost4 and Ost4V23D in micelles. Our studies revealed that while the point mutation did not impact the structure of the protein, it affected its position and solvent exposure in the membrane mimetic environment. Furthermore, our MD simulations of the membrane-bound OST complex containing either WT or V23D mutant demonstrated disruption of most hydrophobic helix-helix interactions between Ost4V23D and transmembrane TM12 and TM13 of Stt3. This disengagement of Ost4V23D from the OST complex led to solvent exposure of the D23 residue in the hydrophobic pocket created by these interactions. Our study not only solves the structures of yeast Ost4 subunit and its mutant but also provides a basis for the destabilization of the OST complex and reduced OST activity.

Preparation of hydrophobic epoxy-polydimethylsiloxane-graphene oxide nanocomposite coatings for antifouling application.

Epoxy-polydimethylsiloxane-graphene oxide (EPG) nanocomposite coatings were successfully developed by loading different wt% of graphene oxide nanosheets (GNs) into an epoxy-hydroxy-terminated-polydimethylsiloxane (EP-hPD) matrix via a facile in situ preparation technique. The inclusion of GNs into EPN led to an increase in modulus of elasticity and tensile strength up to 1570.46 MPa and 31.54 MPa, respectively, in the case of 1 wt% loading of GNs in the EP-hPD matrix. Also, an increase in the water contact angle from 90.1° to 115.2°, 104.5° and 101.7° was discerned at 1, 3 and 5 wt% loadings of GNs respectively. Taber abrasion results demonstrated a decrease in abrasion loss by 33.3% at 1 wt% loading of GNs in comparison to the unreinforced coating. An improvement in the glass transition temperature (Tg) was observed from 63.5 °C for the neat sample to 77.6 °C, 76.3 °C and 71.6 °C for the 1, 3 and 5 wt% EPG nanocomposites, respectively. An inevitable enhancement in the properties of the nanocomposites was affirmed due to the synergistic effect of GNs dispersed within the EP-hPD blend matrix. The prominent findings of this work include a minimum corrosion rate of 0.73 × 10-2 mm per year and upgradation in the antifouling performance of the nanocomposite coatings in comparison to the neat coating.

Development of recycled blends based on cables and wires with plastic cabinets: An effective solution for value addition of hazardous waste plastics.

The recycling of polyvinyl chloride (PVC) recovered from the plastic insulations in wires and cables is a rising concern in the current situation due to its hazardous behaviour during recycling. Similarly, high-impact polystyrene (HIPS) and acrylonitrile butadiene styrene (ABS) used in the structural components of electrical and electronic equipment are also generated in large quantities. In the current work, three agendas were fixed: (a) to determine the effect of recycled polymeric material (HIPS and ABS) recovered from different sources on the mechanical property of the polymeric blends; (b) to formulate a high-impact strength blend; and (c) to deduce a mechanism for improved impact strength. The mechanical characterizations were conducted on the entire blends formulated. Among them, the recycled blend composed of recycled PVC (r-PVC) and recycled ABS (r-ABS) (segregated from uninterrupted power supply housing) and recycled HIPS (r-HIPS; collected from television housing) was confined for further physio-mechanical and thermal analysis. Besides, the r-PVC/r-ABS systems had shown better mechanical properties than r-PVC/r-HIPS systems in similar composition. The impact strength of blend r-PVC/r-ABS (70:30) was found to be 250 J/m, which was 200% more than the blend r-PVC/r-ABS (0:100). The compatibility and non-compatibility in PVC/ABS and PVC/HIPS blends respectively were explained with thermal, mechanical and morphological characterizations. Furthermore, a plausible cross-linking mechanism is developed between ABS and PVC, which controls the release of chlorine atoms into the environment.

Pheromone Perception: Mechanism of the Reversible Coil-Helix Transition in Antheraea polyphemus Pheromone-Binding Protein 1.

Pheromone-binding protein (PBP) in male moth antennae transports pheromone to the olfactory receptor neuron by undergoing a pH-dependent conformational switch, from PBPB at higher pH to PBPA at lower pH, associated with ligand binding and release, respectively. The characteristic feature of the dramatic protein switch is the pH-dependent reversible coil-helix transition of the C-terminus. In the PBPB conformation at pH >6.0, the C-terminus is exposed to the solvent as a coil while the ligand occupies the hydrophobic pocket. However, in the PBPA conformation at acidic pH, the C-terminus switches to a helix and releases the ligand by outcompeting it for the hydrophobic pocket. In Antheraea polyphemus PBP1 (ApolPBP1), the C-terminus (P129-V142) is composed predominantly of hydrophobic residues except for three strategically located acidic residues: Asp132, Glu137, and Glu141. Here, we report for the first time on the consequences of the mutation of one or more acidic residues in the pH-driven reversible coil-helix transition of the ApolPBP1 C-terminus through biophysical characterization. Mutation of any single acidic residue in the C-terminus to its neutral counterpart destabilizes the helix formation at lower pH; these mutants exist as a mixture of both conformations. However, mutation of the two terminal acidic residues together knocks out the protein switch and adversely affects both ligand binding and release functions. Thus, these mutant proteins remain in the open (PBPB) conformation at all pH levels.

Hydrophobic Core Variations Provide a Structural Framework for Tyrosine Kinase Evolution and Functional Specialization.

Protein tyrosine kinases (PTKs) are a group of closely related enzymes that have evolutionarily diverged from serine/threonine kinases (STKs) to regulate pathways associated with multi-cellularity. Evolutionary divergence of PTKs from STKs has occurred through accumulation of mutations in the active site as well as in the commonly conserved hydrophobic core. While the functional significance of active site variations is well understood, relatively little is known about how hydrophobic core variations contribute to PTK evolutionary divergence. Here, using a combination of statistical sequence comparisons, molecular dynamics simulations, mutational analysis and in vitro thermostability and kinase assays, we investigate the structural and functional significance of key PTK-specific variations in the kinase core. We find that the nature of residues and interactions in the hydrophobic core of PTKs is strikingly different from other protein kinases, and PTK-specific variations in the core contribute to functional divergence by altering the stability and dynamics of the kinase domain. In particular, a functionally critical STK-conserved histidine that stabilizes the regulatory spine in STKs is selectively mutated to an alanine, serine or glutamate in PTKs, and this loss-of-function mutation is accommodated, in part, through compensatory PTK-specific interactions in the core. In particular, a PTK-conserved phenylalanine in the I-helix appears to structurally and functionally compensate for the loss of STK-histidine by interacting with the regulatory spine, which has far-reaching effects on enzyme activity, inhibitor sensing, and stability. We propose that hydrophobic core variations provide a selective advantage during PTK evolution by increasing the conformational flexibility, and therefore the allosteric potential of the kinase domain. Our studies also suggest that Tyrosine Kinase Like kinases such as RAF are intermediates in PTK evolutionary divergence inasmuch as they share features of both PTKs and STKs in the core. Finally, our studies provide an evolutionary framework for identifying and characterizing disease and drug resistance mutations in the kinase core.

Correction: Hydrophobic Core Variations Provide a Structural Framework for Tyrosine Kinase Evolution and Functional Specialization.

[This corrects the article DOI: 10.1371/journal.pgen.1005885.].

Influence of non-metallic parts of waste printed circuit boards on the properties of plasticised polyvinyl chloride recycled from the waste wire.

Extreme complexity in the range of metallic and non-metallic parts present in waste printed circuit boards leads to incineration for collecting valuable metals. The non-metallic parts of the printed circuit board can be used effectively without affecting the environment. In this study, the non-metallic parts of the printed circuit board, which is made up by cross-linked resin and fibre, was used as a filler in recycled plasticised polyvinyl chloride collected from waste wires and cables. The properties of the plasticised polyvinyl chloride matrix and plasticised polyvinyl chloride-non-metallic parts of printed circuit board composite were compared with each other by means of mechanical properties and thermal properties. Both mechanical and thermal properties results indicated that incorporation of non-metallic parts of printed circuit board significantly improved the hardness, stiffness, abrasion resistance and thermal stability of plasticised polyvinyl chloride-non-metallic parts of printed circuit board composite; however, the tensile strength of the composite material is not improved because of poor adhesion between the plasticised polyvinyl chloride matrix and non-metallic parts of printed circuit board filler. The poor chemical interaction is also observed from Fourier transform infrared spectroscopy results. This plasticised polyvinyl chloride-non-metallic parts of printed circuit board composite can reduce the leaching of a hazardous element from the printed circuit board with effective utilisation of plastics fraction from waste wires and cables.

Influence of acrylonitrile butadiene rubber on recyclability of blends prepared from poly(vinyl chloride) and poly(methyl methacrylate).

The current investigation deals with the recycling possibilities of poly(vinyl chloride) and poly(methyl methacrylate) in the presence of acrylonitrile butadiene rubber. Recycled blends of poly(vinyl chloride)/poly(methyl methacrylate) are successfully formed from the plastic constituents, those are recovered from waste computer products. However, lower impact performance of the blend and lower stability of the poly(vinyl chloride) phase in the recycled blend restricts its further usage in industrial purposes. Therefore, effective utilisation acrylonitrile butadiene rubber in a recycled blend was considered for improving mechanical and thermal performance. Incorporation of acrylonitrile butadiene rubber resulted in the improvement in impact performance as well as elongation-at-break of the recycled blend. The optimum impact performance was found in the blend with 9 wt% acrylonitrile butadiene rubber, which shows 363% of enhancement as compared with its parent blend. Moreover, incorporated acrylonitrile butadiene rubber also stabilises the poly(vinyl chloride) phase present in the recycled blend, similarly Fourier transform infrared spectroscopy studies indicate the interactions of various functionalities present in the recycled blend and acrylonitrile butadiene rubber. In addition to this, thermogravimetric analysis indicates the improvement in the thermal stability of the recycled blend after the addition of acrylonitrile butadiene rubber into it. The existence of partial miscibility in the recycled blend was identified using differential scanning calorimetry and scanning electron microscopy.

Production and biophysical characterization of a mini-membrane protein, Ost4V23D: A functionally important mutant of yeast oligosaccharyltransferase subunit Ost4p.

N-linked glycosylation of proteins is an essential and highly conserved co- and post-translational protein modification reaction that occurs in all eukaryotes. Oligosaccharyltransferase (OST), a multi-subunit membrane-associated enzyme complex, carries out this reaction. In the central reaction, a carbohydrate group is transferred to the side chain of a consensus asparagine residue in the newly synthesized protein. Genetic defects in humans cause a series of disorders known as congenital disorders of glycosylation (CDG) that include mental retardation, developmental delay, hypoglycemia etc. Complete loss of N-glycosylation is lethal in all organisms. In Saccharomyces cerevisiae, OST consists of nine non-identical protein subunits. Ost4p is the smallest subunit containing 36 residues. It bridges catalytic subunit Stt3p to Ost3p/Ost6p subunit. Mutation of Valine (V) at position 23 in Ost4p to Aspartate (D) causes defects in the N-glycosylation process. To understand the structure, function and role of Ost4p in N-glycosylation, characterization of Ost4p and its functionally important mutant/s are critical. We report the mutagenesis, heterologous overexpression, purification, reconstitution in DPC micelles and biophysical characterization of Ost4V23D and compare its secondary structure and conformation to that of Ost4p. CD and NMR data suggest that mutation of Val23 to Asp impacts the secondary structure and conformation of Ost4p.

Structural and evolutionary divergence of cyclic nucleotide binding domains in eukaryotic pathogens: Implications for drug design.

Many cellular functions in eukaryotic pathogens are mediated by the cyclic nucleotide binding (CNB) domain, which senses second messengers such as cyclic AMP and cyclic GMP. Although CNB domain-containing proteins have been identified in many pathogenic organisms, an incomplete understanding of how CNB domains in pathogens differ from other eukaryotic hosts has hindered the development of selective inhibitors for CNB domains associated with infectious diseases. Here, we identify and classify CNB domain-containing proteins in eukaryotic genomes to understand the evolutionary basis for CNB domain functional divergence in pathogens. We identify 359 CNB domain-containing proteins in 31 pathogenic organisms and classify them into distinct subfamilies based on sequence similarity within the CNB domain as well as functional domains associated with the CNB domain. Our study reveals novel subfamilies with pathogen-specific variations in the phosphate-binding cassette. Analyzing these variations in light of existing structural and functional data provides new insights into ligand specificity and promiscuity and clues for drug design. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.

Predictors of early neurological deterioration in patients with acute ischaemic stroke with special reference to blood urea nitrogen (BUN)/creatinine ratio & urine specific gravity.

BACKGROUND & OBJECTIVES: Early neurological deterioration (END) occurs in about 20 to 40 per cent of patients with acute ischaemic stroke and results in increased mortality and functional disability. In recent studies relative dehydration has been found to be associated with END in patients with acute ischaemic stroke. This study was conducted to identify factors useful for predicting END and to assess the role of blood urea nitrogen/creatinine ratio (BUN/creatinine) and urine specific gravity (USG) as predictors of END in patients with acute ischaemic stroke. METHODS: The present study was an observational prospective study. Various parameters comprising demographic, clinical, laboratory and radiological variables along with stroke severity were assessed and studied as predictors of early neurological deterioration in 114 consecutive patients presenting to the Emergency department during 2012. BUN/creatinine >15 and USG >1.010 were studied as markers of relative dehydration contributing to END. RESULTS: Of the 114 patients enrolled in the study, END was observed in 25 (21.9%) patients. National Institutes Health Stroke Scale score (NIHSS) ≥ 12 at admission was found to be an independent risk factor for END. Amongst markers of relative dehydration, BUN/creatinine >15 at admission was found to be an independent risk factor for END, as also USG >1.010. Also, cerebral oedema and size of hypodensity >1/3 rd of the middle cerebral artery territory on cranial CT were observed to be independent risk factors for END. INTERPRETATION & CONCLUSIONS: Our study findings highlighted a possible association of relative dehydration, as indicated by BUN/creatinine ratio >15, with END along with other parameters like stroke severity at presentation, extent of hypodensity >1/3 rd of the middle cerebral artery (MCA) territory and cerebral oedema. Dehydration being a treatable condition, the use of BUN/creatinine >15 as a marker of relative dehydration, can be helpful in detecting patients with dehydration early and thus play a role in preventing END.

Nano-CeO2 decorated graphene based chitosan nanocomposites as enzymatic biosensing platform: fabrication and cellular biocompatibility assessment.

The present study summarizes the designing of a green transducer phase based on nano-cerium oxide (CeO2) decorated reduced graphene oxide (RGO) reinforced chitosan nanocomposites as an effective enzyme immobilizer and bio-sensing matrix for glucose analyte. Also, it scrutinizes the biocompatibility and cell viability of the synthesized nanohybrid with human fibroblastic macrophage cell line. CeO2 nanoparticles (NPs) were successfully grown on graphene nanosheet in the presence of cationic surfactant followed by facile hydrothermal treatment. The eventual growth of synthesized CeO2 nanocrystals on the graphene layer was confirmed from X-ray diffraction (XRD), transmission electron microscopy (TEM) and Raman analysis. The biocompatibility of the synthesized nanohybrid was also evident from the MTT assay. Glucose oxidase (GOx) was employed on the green polymer nanocomposites modified FTO electrode to fabricate an enzymatic bioelectrode. The electroanalytical response of the GOx/nano-CeO2/RGO/CS/FTO bioelectrode towards electrooxidation of glucose analyte was investigated by electrochemical impedance (EIS) and cyclic voltammetry (CV) study. The resulting biosensor exhibited a good electrochemical response to glucose within the linear detection range of 0.05-6.5 mM with a low detection limit of 2 µM and a sensitivity of 7.198 µA mM(-1) cm(-2). The bioelectrode also showed good shelf life (~10 weeks) and negligible interfering ability under controlled environment. The obtained results indicate that nano-CeO2/RGO nanohybrid based chitosan nanocomposites achieve a biocompatible biosensing platform for effective enzyme immobilization due to the excellent synergistic effects between the CeO2 nanoparticles and graphene sheet.

Clinical & biochemical profile of trichinellosis outbreak in north India.

BACKGROUND & OBJECTIVES: Trichinellosis is a parasitic infection caused by Trichinella nematodes, acquired from consumption of raw meat. However, data from Indian subcontinent are limited. The aim of this study was to investigate the clinical and biochemical profile of a suspected trichinellosis outbreak in a village in Tehri Garhwal district of Uttarakhand state in north India. METHODS: Three index cases presenting as acute febrile myalgia syndrome with eosinophilia, after consumption of uncooked pork in a common feast, were confirmed as trichinellosis on muscle biopsy. A detailed epidemiological survey was carried out in the affected community and all the people who participated in the feast were investigated for clinical and biochemical profile. RESULTS: A total of 54 patients were evaluated in the study. The type of pork consumed included uncooked in 24 per cent (n=13), open fire roasted in 39 per cent (n=21) and fried in 37 per cent (n=20). Clinical symptoms were found in those who consumed pork in uncooked or open fire roasted form (n=34). These included fever with chills and myalgia (100%), periorbital oedema (67%), dyspnoea (9%), and dysphagia (3%). Laboratory parameters studied in both symptomatic and asymptomatic patients showed eosinophilia in 90 per cent (n=41), raised ESR in 98 per cent (n=45), and an elevated creatinine phosphokinase (CPK) level in 85 per cent (n=39). All symptomatic patients were treated with a short course of oral steroids and albendazole therapy. CONCLUSIONS: Trichinella infection is not uncommon in India, and should be suspected in case of acute febrile myalgia especially in areas, where habits of consumption of raw meat is more prevalent.

Recycling of engineering plastics from waste electrical and electronic equipments: influence of virgin polycarbonate and impact modifier on the final performance of blends.

This study is focused on the recovery and recycling of plastics waste, primarily polycarbonate, poly(acrylonitrile-butadiene-styrene) and high impact polystyrene, from end-of-life waste electrical and electronic equipments. Recycling of used polycarbonate, acrylonitrile-butadiene-styrene, polycarbonate/acrylonitrile-butadiene-styrene and acrylonitrile-butadiene-styrene/high impact polystrene material was carried out using material recycling through a melt blending process. An optimized blend composition was formulated to achieve desired properties from different plastics present in the waste electrical and electronic equipments. The toughness of blended plastics was improved with the addition of 10 wt% of virgin polycarbonate and impact modifier (ethylene-acrylic ester-glycidyl methacrylate). The mechanical, thermal, dynamic-mechanical and morphological properties of recycled blend were investigated. Improved properties of blended plastics indicate better miscibility in the presence of a compatibilizer suitable for high-end application.

Advancing sustainable agriculture: Evaluation of Poly (lactic acid) (PLA) based mulch films and identification of biodegrading microorganisms among soil microbiota.

Non-biodegradable polyolefin based plastic mulch residues in agricultural fields after the end of a crop cycle have raised several concerns as an environmental pollutant in recent years. This study explores the potential of Poly (lactic acid) (PLA) and Poly (butylene adipate-co-terephthalate) (PBAT) based compostable films reactively blended with compatibilizers and chain extenders as a promising solution to environmental challenges associated with traditional plastic mulch films. Epoxidized soybean oil (ESO) and Epoxy-functionalized styrene acrylic copolymer (ESA) have been used as reactive compatibilizers and chain extenders respectively. In-depth analysis of the mechanical, thermal, and barrier properties of the developed films, revealed that the PLA/PBAT blend films at 75:25 weight ratio in the presence of 5 phr ESO and 0.5 phr ESA exhibit improved performance characteristics for application as mulch films. Furthermore, the films were subjected to 360-h UV exposure to gauge their stability under prolonged exposure, specifically investigating changes in the carbonyl index. Additionally, a rigorous real-time field trial of the mulch films spanning eight months with various crops was carried out to understand their performance in practical agricultural settings. The study also involved the identification of microorganisms responsible for the degradation of the developed mulch films employing 16S rRNA sequencing.

Structural insights into the ligand binding and releasing mechanism of Antheraea polyphemus pheromone-binding protein 1: role of the C-terminal tail.

Pheromone-binding proteins (PBPs) in lepidopteran moths selectively transport the hydrophobic pheromone molecules across the sensillar lymph to trigger the neuronal response. Moth PBPs are known to bind ligand at physiological pH and release it at acidic pH while undergoing a conformational change. Two molecular switches are considered to play a role in this mechanism: (i) protonation of His(70) and His(95) situated at one end of binding pocket and (ii) switch of the unstructured C-terminus at the other end of the binding pocket to a helix that enters the pocket. We have reported previously the role of the histidine-driven switch in ligand release for Antheraea polyphemus PBP1 (ApolPBP1). Here we show that the C-terminus plays a role in the ligand release and binding mechanism of ApolPBP1. The C-terminus truncated mutants of ApolPBP1 (ApolPBP1ΔP129-V142 and ApolPBP1H70A/H95AΔP129-V142) exist only in the bound conformation at all pH levels, and they fail to undergo pH- or ligand-dependent conformational switching. Although these proteins could bind ligands even at acidic pH unlike wild-type ApolPBP1, they had ~4-fold reduced affinity for the ligand at both acidic and physiological pH compared to that of wild-type ApolPBP1 and ApolPBP1H70A/H95A. Thus, apart from helping in ligand release at acidic pH, the C-terminus in ApolPBP1 also plays an important role in ligand binding and/or locking the ligand in the binding pocket. Our results are in stark contrast to those reported for BmorPBP and AtraPBP, where C-terminus truncated proteins had similar or increased pheromone binding affinity at any pH.