Molecular forces governing protein-protein interaction: Structure-function relationship of complexes protein in the food industry.

The application of protein-protein interaction (PPI) has been widely used in various industries, such as food, nutraceutical, and pharmaceutical. A deeper understanding of PPI is needed, and the molecular forces governing proteins and their interaction must be explained. The design of new structures with improved functional properties, e.g., solubility, emulsion, and gelation, has been fueled by the development of structural and colloidal building blocks. In this review, the molecular forces of protein structures are discussed, followed by the relationship between molecular force and structure, ways of a bind of proteins together in solution or at the interface, and functional properties. A more detailed look is thus taken at the relationship between the various influencing factors on molecular forces involved in PPI. These factors include protein properties, such as types, concentration, and mixing ratio, and solvent conditions, such as ionic strength and pH. This review also summarizes methods tha1t are capable of identifying molecular forces in protein and PPI, as well as characterizing protein structure.

A Trichinella spiralis new born larvae-specific protein, Ts-NBL1, interacts with host's cell vimentin.

The parasitic nematode Trichinella has a special relationship with its host as it has a unique intracellular location within the feeder cell which is a structure derived from skeletal muscle fiber. It has been proposed that "parakines" secreted by Trichinella larvae serve as messengers to implement communication between the parasite and the muscle cells through a molecular cross-talk to ensure permanent coexistence within the host. The Ts-NBL1 protein is considered to be a potential key "parakine" involved in the early invasion of the muscle fiber and its transformation into a feeder cell during Trichinella spiralis infection. This study used for the first time yeast two-hybrid (Y2H) technology in Trichinella to identify Ts-NBL1 interacting proteins. GST co-affinity purification experiments confirmed vimentin as an important interactor. The discovery of the new host proteins interacting with Ts-NBL1 will help to suggest that Ts-NBL1 contributes to participate in the capsule formation of feeder cells and provide ideas for understanding the molecular and cellular mechanisms involved in the survival of Trichinella in the host.

The division protein FtsZ interacts with the small heat shock protein IbpA in Acholeplasma laidlawii.

Small heat shock proteins (sHSPs) control the proteins stability in the cell preventing their irreversible denaturation. While many mycoplasmas possess the sHSP gene in the genome, Acholeplasma laidlawii is the only mycoplasma capable of surviving in the environment. Here we report that the sHSP IbpA directly interacts with the key division protein FtsZ in A. laidlawii, representing the first example of such interaction in prokaryotes. FtsZ co-immunoprecipitates with IbpA from A. laidlawii crude extract and in vitro binds IbpA with KD ~ 1 µM. Proteins co-localize in the soluble fraction of the cell at 30-37 °C and in the non-soluble fraction after 1 h exposition to cold stress (4 °C). Under heat shock conditions (42 °C) the amount of FtsZ decreases and the protein remains in both soluble and non-soluble fractions. Furthermore, in vitro, FtsZ co-elutes with IbpAHis6 from A. laidlawii crude extract at any temperatures from 4 to 42 °C, with highest yield at 42 °C. Moreover, in vitro FtsZ retains its GTPase activity in presence of IbpA, and the filaments and bundles formation seems to be even improved by sHSP at 30-37 °C. At extreme temperatures, either 4 or 42 °C, IbpA facilitates FtsZ polymerization, although filaments under 4 °C appears shorter and with lower density, while at 42 °C IbpA sticks around the bundles, preventing their destruction by heat. Taken together, these data suggest that sHSP IbpA in A. laidlawii contributes to the FtsZ stability control and may be assisting appropriate cell division under unfavorable conditions.

Identification of Key Potential Targets and Pathway for Arsenic Trioxide by Systemic Bioinformatics Analysis in Pancreatic Cancer.

Arsenic trioxide is an approved chemotheraputic agent for the treatment of acute promyelocytic leukemia (APL). Recently, numerous studies suggested that arsenic trioxide acts as anti-cancer roles in various human malignancies. However, the molecular mechanisms are not fully elucidated. In this study, we explored the critical targets of arsenic trioxide and their interaction network systematically by searching the publicly available published database like DrugBank (DB) and STRING. Seven direct protein targets (DPTs) and 111 DPT-associated genes were identified. The enrichment analysis of arsenic trioxide associated genes/proteins revealed 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Among these pathways, phosphatidylinositol-4,5-bisphosphate-3-kinase -Akt (PI3K-Akt) single pathway and pancreatic cancer pathway are highly correlated with arsenic trioxide and have 5 overlapped targets. Then we investigated the gene alternation of selected critical genes in pancreatic cancer studies using cBio portal. These results indicated that arsenic trioxide could act anti-tumor function through PI3K-Akt single pathway and identified critical genes might be therapeutic targets for pancreatic cancer.

Monitoring drug-serum protein interactions for early ADME prediction through Surface Plasmon Resonance technology.

Many molecules fail to reach the market due to poor pharmacokinetic (PK) properties, rendering the potential drug virtually unavailable for the primary target despite efficient administration to the body. PK properties of endogenous and exogenous compounds in mammals are dependent, among other factors, on their ability to interact with serum proteins. The extent of binding can greatly influence their ADME (adsorption, distribution, metabolism and execration) profile. Reliable and cost-effective bioavailability studies, early in the drug discovery process, can lead to an improvement of the success rate for compounds entering clinical trials. Optical biosensors based on surface plasmon resonance (SPR) detection emerged as an efficient approach to obtain large amounts of information about the binding of small molecules to serum proteins. Simple, automated and fast assays provide a good throughput, versatility and highly informative data output, rendering the methodology particularly suited for early screening. The ability to provide basic information on PK can be easily coupled to structure-activity relationship analysis. In this review, features of the technology and its employment for the study of serum protein-small molecule interactions are presented and discussed.

Insights into B-type RR members as signaling partners acting downstream of HPt partners of HK1 in the osmotic stress response in Populus.

The B-type response regulators (B-type RRs), final elements of a signaling pathway called "histidine/aspartate phosphorelay system" in plants, are devoted to the regulation of response genes through a transcription factor activity. Signal transduction consists in the transfer of a phosphoryl group from a transmembrane histidine kinase (HK) which recognizes a given stimulus to nuclear RRs via cytosolic shuttle phosphotransfer proteins (HPts). In Arabidopsis, the receptors HK are to date the major characterized candidates to be responsible for initiation of osmotic stress responses. However, little information is available concerning the signaling partners acting downstream of HKs. In Populus, three HPts and five B-type RRs were previously identified as interacting partners of HK1, the Arabidopsis AHK1 homolog. Here, we report the isolation of RR18, a member of the B-type RR family, which shares high sequence similarities with ARR18 characterized to act in the osmosensing signaling pathway in Arabidopsis, from poplar cuttings subjected to osmotic stress conditions. By using yeast and in planta interaction assays, RR18 was further identified as acting downstream of HK1 and its three preferential HPt partners. Besides, our results are in favor of a possible involvement of both RR18 and RR13, the main expressed poplar B-type RR, in the osmotic signaling pathway. Nonetheless, different behaviors of these two B-type RRs in this pathway need to be noted, with one RR, RR13, acting in an early phase, mainly in roots of poplar cuttings, and the other one, RR18, acting in a late phase, mainly in leaves to supply an adequate response.