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1.
JMIR Med Inform ; 8(5): e17645, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32436854

RESUMO

BACKGROUND: Knowledge graph embedding is an effective semantic representation method for entities and relations in knowledge graphs. Several translation-based algorithms, including TransE, TransH, TransR, TransD, and TranSparse, have been proposed to learn effective embedding vectors from typical knowledge graphs in which the relations between head and tail entities are deterministic. However, in medical knowledge graphs, the relations between head and tail entities are inherently probabilistic. This difference introduces a challenge in embedding medical knowledge graphs. OBJECTIVE: We aimed to address the challenge of how to learn the probability values of triplets into representation vectors by making enhancements to existing TransX (where X is E, H, R, D, or Sparse) algorithms, including the following: (1) constructing a mapping function between the score value and the probability, and (2) introducing probability-based loss of triplets into the original margin-based loss function. METHODS: We performed the proposed PrTransX algorithm on a medical knowledge graph that we built from large-scale real-world electronic medical records data. We evaluated the embeddings using link prediction task. RESULTS: Compared with the corresponding TransX algorithms, the proposed PrTransX performed better than the TransX model in all evaluation indicators, achieving a higher proportion of corrected entities ranked in the top 10 and normalized discounted cumulative gain of the top 10 predicted tail entities, and lower mean rank. CONCLUSIONS: The proposed PrTransX successfully incorporated the uncertainty of the knowledge triplets into the embedding vectors.

2.
Cell Mol Life Sci ; 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32318758

RESUMO

Faithful chromosome segregation during mitosis requires the correct assembly of kinetochore on the centromere. CENP-A is a variant of histone H3, which specializes the centromere region on chromatin and mediates the kinetochore assembly. The Mis18 complex plays a critical role in initiating the centromere loading of the newly-synthesized CENP-A. However, it remains unclear how Mis18 complex (spMis18, spMis16 and spMis19) is located to the centromere to license the recruitment of Cnp1CENP-A in Schizosaccharomyces pombe. We found that spMis18 directly binds to nucleosomal DNA through its extreme C-terminus and interacts with H2A-H2B dimer via the acidic region on the surface of its Yippee-like domain. Live-cell imaging confirmed that mutation of the acidic region and deletion of the extreme C-terminus significantly impairs the localization of spMis18 and Cnp1 to the centromere and delays chromosome segregation during mitosis. Our findings illustrate that the interaction of spMis18 with histone H2A-H2B and DNA plays important roles in the recruitment of spMis18 and Cnp1 to the centromere in fission yeast.

3.
J Ethnopharmacol ; 257: 112862, 2020 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-32294507

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniflorin, a prominent component in some Chinese formulas for hyperprolactinemia-associated disorders, has been found to inhibit prolactin secretion in prolactinoma cells. AIM: To examine the efficacy of paeoniflorin on hyperprolactinemia and the underlying mechanisms of action. MATERIALS AND METHODS: Hyperprolactinemia in female rats was generated by administration of olanzapine (5 mg/kg, by a gavage method, once daily, × 13 weeks). The rats were co-treated with paeoniflorin (10 and 50 mg/kg). Prolactin and TGF-ß1 concentrations were detected by ELISA. Protein expression was determined by Western blot. The effect in MMQ cells was also examined. RESULTS: Paeoniflorin inhibited olanzapine-induced increases in plasma prolactin concentration and prolactin protein overexpression in the pituitary and hypothalamus of rats. Further, paeoniflorin restored olanzapine-induced downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein expression. More importantly, paeoniflorin attenuated olanzapine-suppressed protein expression of transforming growth factor (TGF)-ß1 and its downstream genes, type II TGF-ß receptor, type I TGF-ß receptor and phosphorylated SMAD3 in the tissues. However, paeoniflorin did not affect plasma TGF-ß1 concentration and hepatic TGF-ß1 protein expression. In accord, olanzapine-induced increase in prolactin concentration, upregulation of prolactin protein expression, and downregulation of protein expression of the D2R and TGF-ß1 signals in MMQ cells were attenuated. CONCLUSIONS: This study demonstrates that paeoniflorin ameliorates olanzapine-induced hyperprolactinemia in rats by attenuating impairment of the D2R and TGF-ß1 signaling pathways in the hypothalamus and pituitary. Our findings may provide evidence to support the use of paeoniflorin-contained Chinese herbs and formulas for hyperprolactinemia and its associated disorders.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32039576

RESUMO

Li has been regarded as the most attractive anode for next-generation high-energy-density batteries due to its high specific capacity and low electrochemical potential. However, its low electrochemical potential leads to the side reaction of Li with the solvent of the electrolyte (the solvation of Li ions exacerbates the reaction). This adverse side reaction results in uneven Li distribution and deposition, low Coulombic efficiency, and the formation of Li dendrites. Herein, we demonstrate an efficient method for achieving successive desolvation and homogeneous distribution of Li ions by using a double-layer membrane. The first layer is designed to enable the desolvation of Li ions. The second layer with controllable and ordered nanopores is expected to facilitate the homogeneous and exclusive transport of Li ions. The efficiency of the double-layer membrane on desolvation and exclusive transport of Li ions is confirmed by theoretical calculations, the significantly enhanced Li-ion transference number, improved Coulombic efficiency, and the inhibition of Li dendrites. These results will deepen our understanding of the modulation of ions and pave a way to the next-generation high-energy-density Li-metal batteries.

5.
New Phytol ; 226(4): 1042-1054, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31917861

RESUMO

Cellular abscisic acid (ABA) concentration is determined by both de novo biosynthesis and recycling via ß-glucosidase(s). However, which rice ß-glucosidase(s) are involved in this process remains unknown. Here, we report on a chloroplastic ß-glucosidase isoenzyme, Os3BGlu6, that functions in ABA recycling in rice. Disruption of Os3BGlu6 in rice resulted in dwarfism, lower ABA content in leaves, drought-sensitivity, lower photosynthesis rate and higher intercellular CO2 concentration. Os3BGlu6 could hydrolyze ABA-GE to ABA in vitro. The reversion and overexpression rice lines restored or increased the drought tolerance as shown by the higher ß-glucosidase activity, ABA concentrations and expressions of ABA- and drought-responsive genes. Drought induced Os3BGlu6 to form dimers, and the degree of polymerization correlated well with the increase in cellular ABA concentrations and drought tolerance in rice. Os3BGlu6 was responsive to drought and ABA treatments, and the protein was localized to the chloroplast. Disruption of Os3BGlu6 resulted in the increased stomatal density and impaired stomatal movement. Transcriptomics revealed that disruption of Os3BGlu6 resulted in chloroplastic oxidative stress and lowered Rubisco activity even under normal conditions. Taken together, these results suggest that chloroplastically localized Os3BGlu6 significantly affects cellular ABA pools, thereby affecting drought tolerance and photosynthesis in rice.

6.
Sci Rep ; 10(1): 480, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949226

RESUMO

Collective decision-making is important for coordination and synchronization of the activities among group-living animals and the mechanisms guiding such procedure involve a great variety of characteristics of behavior and motivation. This study provides some evidence investigating collective movement initiation in a multi-level social band of the golden snub-nosed monkeys (Rhinopithecus roxellana) located in the Mts. Qinling, China. We collect 1223 datum records relevant to decision initiation from six OMUs. The results indicate that collective movement initiation could be divided into two continual but relatively independent processes: decisions on moving direction and movement implementation. In both processes, adult individuals are more likely to initiate the decision-making, while other adults vote on initiator's preference, with a threshold, a supporting number required for a success. Thus, voting behavior and quorum fulfillment contribute to a successful decision-making. Adult individuals play important role in making decisions for moving direction and implementation. For a successful collective movement initiation, the individuals being more central in grooming network initiate decisions more frequently than the others, and attract voters more easily. Furthermore, following the initiation, at least four positive voters are required for a direction decision and at least three positive voters are needed for the decision on movement implementation, which could be considered as the threshold of quorum numbers required for a successful decision. This study has provided some very interesting information and scientific evidence in understanding social structure and behaviors of the nonhuman primates with a social structure very similar to humans'. Thus, some results can directly be referred to the comprehension of human social structure and behavior.

7.
Biotechnol Lett ; 42(5): 787-795, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31970556

RESUMO

Staphylococcus aureus is an anaerobic facultative microorganism that features the NreABC system for nitrate respiration. NreB is the sensor histidine kinase that phosphorylates the response regulator NreC to stimulate the expression of target genes. NreA is a nitrate sensor which dissociates from NreB in the present of nitrate and relieves its inhibition on NreB. However, the molecular basis of how NreA regulate NreB remains unknown. In this study, we determined the crystal structures of nitrate-bound NreA from S. aureus (SaNreA/NO3-) and its apoNreA-like mutant SaNreAY94A in complex with ethanediol (SaNreAY94A/EDO). Structural comparison reveals that the C-terminal loop in SaNreA/NO3- rearranges to an α-helix (α7) in SaNreAY94A/EDO, which converts an acidic pocket on the surface to a positively charged region. This conformational change of SaNreA C-terminus might play a role in SaNreB binding.

8.
Small ; : e1907172, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31967725

RESUMO

Structural symmetry is a simple way to quantify the anisotropic properties of materials toward unique device applications including anisotropic transportation and polarization-sensitive photodetection. The enhancement of anisotropy can be achieved by artificial symmetry-reduction design. A core-shell SbI3 /Sb2 O3 nanowire, a heterostructure bonded by van der Waals forces, is introduced as an example of enhancing the performance of polarization-sensitive photodetectors via symmetry reduction. The structural, vibrational, and optical anisotropies of such core-shell nanostructures are systematically investigated. It is found that the anisotropic absorbance of a core-shell nanowire is obviously higher than that of two single compounds from both theoretical and experimental investigations. Anisotropic photocurrents of the polarization-sensitive photodetectors based on these core-shell SbI3 /Sb2 O3 van der Waals nanowires are measured ranging from ultraviolet (UV) to visible light (360-532 nm). Compared with other van der Waals 1D materials, low anisotropy ratio (Imax /Imin ) is measured based on SbI3 but a device based on this core-shell nanowire possesses a relatively high anisotropy ratio of ≈3.14 under 450 nm polarized light. This work shows that the low-symmetrical core-shell van der Waals heterostructure has large potential to be applied in wide range polarization-sensitive photodetectors.

9.
J Ethnopharmacol ; 254: 112572, 2020 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31940455

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Antipsychotics often induce hyperprolactinemia. The transforming growth factor (TGF)-beta1 signaling in the pituitary and hypothalamus inhibits prolactin synthesis and secretion, and its impairment is implicated in neuropsychiatric disorders. Longdan Xiegan Tang (LXT) alone or together with antipsychotics have been used to treat various neuropsychiatric diseases and hyperprolactinemia-associated disorders. AIM OF THE STUDY: To investigate the effect of LXT on hyperprolactinemia and involvement of the TGF-beta1 signaling. MATERIALS AND METHODS: Male rats were co-administered with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) (p.o., × 8 weeks). Plasma concentrations of prolactin and TGF-beta1 were determined by ELISA. Protein expression was analyzed by Western blot. RESULTS: Treatment of rats with LXT extract suppressed olanzapine-induced increase in plasma prolactin concentration and overexpression of pituitary and hypothalamic prolactin protein. Importantly, LXT restored olanzapine-induced decrease in protein expression of the key components of the TGF-beta1 signaling, TGF-beta1, type II TGF-beta receptor, type I TGF-beta receptor and phosphorylated SMAD3 in the pituitary and hypothalamus. Further, it antagonized downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein level, and inhibited pituitary estrogen receptor (ER) alpha and ERbeta protein expression. CONCLUSIONS: The present results suggest that LXT ameliorates antipsychotic-induced hyperprolactinemia in rats by repairing the pituitary and hypothalamic TGF-beta1 signaling possibly via D2R, ERs or/and other pathways. Our findings may also provide scientific elucidation for use of the ancient Chinese formula to treat the impaired TGF-beta1 signaling-associated neuropsychiatric disorders.

10.
Chem Asian J ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714679

RESUMO

Alternatives of commercial lithium-ion batteries (LIBs) have drawn huge attention due to the large demand of energy storage systems and the lack of resources for traditional LIBs. Promising candidates include but are not limited to Li-S batteries, organic batteries and flow batteries. However, the dissolution of active materials and the consequent shuttle effect, as one of the main challenges in these candidates, always leads to significant capacity loss and poor cycling life. The rising two-dimensional (2D) materials, with well-defined structures and attractive physical and chemical properties, provide a new vision to solve these problems via suppressing the shuttle of the dissolved active materials. Herein, we present a minireview on the advances and perspectives of 2D materials as ionic sieves for inhibiting the shuttle effect in batteries.

11.
Angew Chem Int Ed Engl ; 58(41): 14731-14739, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31381218

RESUMO

π-d Conjugated coordination polymers (CCPs) have attracted much attention for various applications, although the chemical states and structures of many CCPs are still blurry. Now, a one-dimensional (1D) π-d conjugated coordination polymer for high performance sodium-ion batteries is presented. The chemical states of the obtained coordination polymer are clearly revealed. The electrochemical process undergoes a three-electron reaction and the structure transforms from C=N double bonds and NiII to C-N single bonds and NiI , respectively. Our unintentional experiments provided visual confirmation of NiI . The existence of NiI was further corroborated by its X-ray absorption near-edge structure (XANES) and its catalytic activity in Negishi cross-coupling.

12.
Chem Commun (Camb) ; 55(73): 10856-10859, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31441926

RESUMO

Conjugated coordination polymers (CCPs), showing high conductivity, can be expected to be possibly applied in batteries, which, however, have not been well studied. Furthermore, CCPs are so unique that most of their chemical structures have not been well determined. Herein, a highly conductive CCP is reported for sodium-ion batteries, which shows high rate performance and high capacity retention of 84% even at 30C. What's more, the chemical structure is successfully revealed based on the structure variation during the electrochemical redox process.

13.
Ying Yong Sheng Tai Xue Bao ; 30(2): 627-636, 2019 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-30915815

RESUMO

Land carrying capacity is one of the important research fields for land management and sustainable use. Urban-rural construction land is an essential component of land use type, the rationality of whose structure and layout is crucial to the sustainable use of land. Here, we executed the evaluation of the suitability of urban-rural construction land development, accounted the bearable critical threshold of urban-rural construction land, calculated the bearable abundance of urban-rural construction land, and compared with the current urban-rural construction land, analyzed the matching of the space layout, and then obtained the remaining development intensity of each county (city or district) of the Poyang Lake urban agglomeration. The results showed that the most suitable, more suitable, less suitable and unsuitable area about the evaluation results of urban-rural construction land development suitability were 3130.62, 2477.29, 867.03 and 29509.14 km2, respectively. The bearable critical threshold of urban-rural construction land (developable strength) was 16.6%, and the value of each county (city, district) was 7.7%-100%. The abundance of urban-rural construction land in each county (city, district) was mainly 0.15-1.30. The remaining development intensity was 12.3%, and the spatial matching degree was 0.76. The remaining develo-pment intensity of each county (city, district) was 4.9%-53.5%, and the spatial matching degree of each county (city, district) was 0.11- 1.00, with a wide range. Our results would help to clarify the relationship between the current development status and the rational development status, which could provide a basis for the refined management of urban-rural construction land and the regulatory policies' formulation of spatial pattern optimization.


Assuntos
Lagos , China , Cidades , Conservação dos Recursos Naturais
14.
Biochem J ; 476(2): 211-223, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30523058

RESUMO

Histone modification is a ubiquitous regulatory mechanism involved in a variety of biological processes, including gene expression, DNA damage repair, cell differentiation, and ontogenesis. Succinylation sites on histones have been identified and may have functional consequences. Here, we demonstrate that human sirtuin 5 (Sirt5) catalyzes the sequence-selective desuccinylation of numerous histone succinyl sites. Structural studies of Sirt5 in complex with four succinyl peptides indicate an essential role for the conserved main chain hydrogen bonds formed by the succinyl lysine (0), +1, and +3 sites for substrate-enzyme recognition. Furthermore, biochemical assays reveal that the proline residue at the +1 site of the histone succinylation substrate is unfavorable for Sirt5 interaction. Our findings illustrate the molecular mechanism underlying the sequence-selective desuccinylase activity of Sirt5 and provide insights for further studies of the biological functions associated with histone succinylation and Sirt5.


Assuntos
Histonas/química , Peptídeos/química , Processamento de Proteína Pós-Traducional , Sirtuínas/química , Ácido Succínico/química , Histonas/genética , Histonas/metabolismo , Humanos , Peptídeos/genética , Peptídeos/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismo , Relação Estrutura-Atividade , Ácido Succínico/metabolismo
15.
Zool Res ; 40(2): 129-138, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30559334

RESUMO

Golden snub-nosed monkeys (Rhinopithecus roxellana), as typical arboreal group-living Old World monkeys, provide an appropriate animal model to research manual laterality and explore the factors affecting hand preference in nonhuman primates. This study investigated hand preference based on 63 subjects and four spontaneous manual tasks (including unimanual and bimanual feeding and grooming), and assessed the effects of age, gender and type of task on handedness in R. roxellana. A population-level left-handedness was found not only in the bimanual coordinated tasks (bimanual feeding and grooming), but also in one unimanual reaching task (unimanual feeding). There were no significant differences between the sexes in either direction or strength of hand preference among any task. However, a significant difference between adults and juveniles was found in the unimanual feeding task. This is the first report on handedness in unimanual and bimanual feeding tasks that require bipedal posture in wild R. roxellana. Furthermore, this study demonstrated spontaneous feeding tasks reported previously only in the quadrupedal posture in this species, supporting the importance of factors such as posture and task complexity in the evolution of primate manual lateralization.


Assuntos
Envelhecimento , Colobinae/fisiologia , Lateralidade Funcional/fisiologia , Animais , Feminino , Masculino , Fatores Sexuais
16.
FEBS Lett ; 592(24): 4098-4110, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30381828

RESUMO

Using methods combining cross-linking, pull-down assays, and stable isotope labeling by amino acids in cell culture with mass spectrometry, we identified that the Tudor domain-containing protein Spindlin-1 recognizes trimethylation of histone H4 lysine 20 (H4K20me3). The binding affinity of Spindlin-1 to H4K20me3 is weaker than that to H3K4me3, indicating H4K20me3 as a secondary substrate for Spindlin-1. Structural studies of Spindlin-1 in complex with the H4K20me3 peptide indicate that Spindlin-1 attains a distinct binding mode for H4K20me3 recognition. Further biochemical analysis identified that Spindlin-1 also binds methylated R23 of H4, providing new clues for the function of Spindlin-1.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Histonas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Fosfoproteínas/metabolismo , Arginina/química , Arginina/metabolismo , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Cristalografia por Raios X , Células HeLa , Histonas/química , Humanos , Lisina/química , Lisina/metabolismo , Metilação , Proteínas Associadas aos Microtúbulos/química , Proteínas Associadas aos Microtúbulos/genética , Modelos Moleculares , Mutação , Fosfoproteínas/química , Fosfoproteínas/genética , Ligação Proteica , Domínios Proteicos
17.
Acta Crystallogr F Struct Biol Commun ; 74(Pt 11): 704-709, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30387775

RESUMO

CshA is a DEAD-box RNA helicase that belongs to the DExD/H-box family of proteins, which generally have an RNA-dependent ATPase activity. In Staphylococcus aureus, CshA was identified as a component of the RNA degradosome and plays important roles in RNA turnover. In this study, the crystal structures of the N-terminal RecA-like domain 1 of S. aureus CshA (SaCshAR1) and of its complex with AMP (SaCshAR1-AMP) are reported at resolutions of 1.5 and 1.8 Å, respectively. SaCshAR1 adopts a conserved α/ß RecA-like structure with seven parallel strands surrounded by nine α-helices. The Q motif and motif I are responsible for the binding of the adenine group and phosphate group of AMP, respectively. Structure comparison of SaCshAR1-AMP and SaCshAR1 reveals that motif I undergoes a conformational change upon AMP binding. Isothermal titration calorimetry assays further conformed the essential roles of Phe22 in the Q motif and Lys52 in motif I for binding ATP, indicating a conserved substrate-binding mechanism in SaCshA compared with other DEAD-box RNA helicases.


Assuntos
Monofosfato de Adenosina/metabolismo , Proteínas de Bactérias/química , RNA Helicases DEAD-box/química , Staphylococcus aureus/enzimologia , Adenina/metabolismo , Monofosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Motivos de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Varredura Diferencial de Calorimetria , Cristalografia por Raios X , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Lisina/química , Lisina/genética , Lisina/metabolismo , Modelos Moleculares , Mutagênese , Fenilalanina/química , Fenilalanina/genética , Fenilalanina/metabolismo , Domínios Proteicos
18.
Angew Chem Int Ed Engl ; 57(49): 16072-16076, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30295985

RESUMO

The shuttle effect of electrode materials always leads to capacity loss and poor cycle life of batteries. Two-dimensional (2D) covalent organic frameworks (COFs) with uniform and controllable nanopores provide a promising strategy for fabricating ionic sieves to inhibit the shuttle effect. However, the insoluble nature of COFs made it difficult to fabricate compact and ordered membranes of COFs. Herein, we report a novel method for facilely anisotropic ordering of 2D COFs via depositing COFs onto graphene. The resulted double-layer membranes acting as ionic sieves impressively inhibit the shuttle effect and exhibit versatility to both organic sodium-ion batteries and Li-S batteries, leading to high cyclability.

19.
Curr Zool ; 64(4): 441-447, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30108624

RESUMO

In social mammals, kinship is an important factor that often affects the interactions among individuals within groups. In primates that live in a multilevel society, kinship may affect affiliative patterns between individuals at different scales within the larger group. For this study, we use field observations and molecular methods to reveal the profiles of how kinship affects affiliative behaviors between individuals in a breeding band of wild golden snub-nosed monkeys (Rhinopithecus roxellana). We use a novel nonparametric test, the partition Mantel test, to measure independently the correlation between kinship and each of three affiliative behaviors. Our results show that more closely related females are more likely to groom each other. Average relatedness between adult females within the same one-male unit (OMU) is higher than that between adult females from different OMUs. We suggest that closely related females may reside in the same OMU in order to attain inclusive fitness benefits, and that kinship plays an important role in maintaining the social structure of this species.

20.
Biochem Biophys Res Commun ; 503(3): 1207-1213, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30005877

RESUMO

RNase HII exists ubiquitously in organisms and functions as a monomer in prokaryotes. We determined the crystal structure of Staphylococcus aureus RNase HII (Sa-RNase HII), which displays a novel dimer conformation, with the active site of each monomer covered by the other one. Both small-angle X-ray scattering and gel-filtration analysis confirmed that Sa-RNase HII exists as a homodimer in solution. Enzymatic analysis revealed that the "self-inhibited" dimeric form is catalytically active. Furthermore, continuous-wave electron paramagnetic resonance experiments clarified that the Sa-RNase HII dimer undergoes a large conformational change upon substrate binding, but remains a dimer to catalyze the reaction. Our structural and biochemical studies identified a novel functional dimer of Sa-RNase HII with distinct regulation mechanism for its catalytic activity.


Assuntos
Ribonuclease H/química , Ribonuclease H/metabolismo , Staphylococcus aureus/enzimologia , Sequência de Aminoácidos , Cromatografia em Gel , Clonagem Molecular , Cristalografia por Raios X , Dimerização , Modelos Moleculares , Conformação Proteica , Ribonuclease H/genética , Alinhamento de Sequência
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