Protein Science最新文献

{"title":"AlphaFold2's training set powers its predictions of some fold-switched conformations.","authors":"Joseph W Schafer, Lauren L Porter","doi":"10.1002/pro.70105","DOIUrl":"10.1002/pro.70105","url":null,"abstract":"<p><p>AlphaFold2 (AF2), a deep-learning-based model that predicts protein structures from their amino acid sequences, has recently been used to predict multiple protein conformations. In some cases, AF2 has successfully predicted both dominant and alternative conformations of fold-switching proteins, which remodel their secondary and/or tertiary structures in response to cellular stimuli. Whether AF2 has learned enough protein folding principles to reliably predict alternative conformations outside of its training set is unclear. Previous work suggests that AF2 predicted these alternative conformations by memorizing them during training. Here, we use CFold-an implementation of the AF2 network trained on a more limited subset of experimentally determined protein structures-to directly test how well the AF2 architecture predicts alternative conformations of fold switchers outside of its training set. We tested CFold on eight fold switchers from six protein families. These proteins-whose secondary structures switch between α-helix and β-sheet and/or whose hydrogen bonding networks are reconfigured dramatically-had not been tested previously, and only one of their alternative conformations was in CFold's training set. Successful CFold predictions would indicate that the AF2 architecture can predict disparate alternative conformations of fold-switched conformations outside of its training set, while unsuccessful predictions would suggest that AF2 predictions of these alternative conformations likely arise from association with structures learned during training. Despite sampling 1300-4300 structures/protein with various sequence sampling techniques, CFold predicted only one alternative structure outside of its training set accurately and with high confidence while also generating experimentally inconsistent structures with higher confidence. Though these results indicate that AF2's current success in predicting alternative conformations of fold switchers stems largely from its training data, results from a sequence pruning technique suggest developments that could lead to a more reliable generative model in the future.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 4","pages":"e70105"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine-tuned interactions between globular and disordered regions of single-stranded DNA binding (SSB) protein are required for dynamic condensation under physiological conditions.","authors":"Zoltán J Kovács, Péter Ecsédi, Gábor M Harami, János Pálinkás, Mina Botros, Lamiya Mahmudova, Viktoria Katran, Dávid Érfalvy, Miklós Cervenak, László Smeller, Mihály Kovács","doi":"10.1002/pro.70109","DOIUrl":"10.1002/pro.70109","url":null,"abstract":"<p><p>Increasing evidence points to the importance of liquid-liquid phase separation (LLPS)-driven protein condensation in both eukaryotic and bacterial cell physiology. The formation of condensates may involve interactions between both structured (globular) domains and intrinsically disordered protein regions and requires multivalency that is often brought about by oligomerization. Here we dissect such contributions by assessing engineered variants of bacterial (Escherichia coli) single-stranded DNA binding (SSB) protein whose condensation has recently been implicated in bacterial genome metabolism. A truncated SSB variant (SSBdC, lacking the conserved C-terminal peptide (CTP)) was used to assess the importance of interactions between SSB's globular oligonucleotide/oligosaccharide binding (OB) domain and the CTP. We show that OB-CTP interactions are essential for dynamic condensation in physiological (crowded, glutamate-rich) environments. Via assessment of a protein variant (SSB^H55Y) from the known thermosensitive ssb-1 mutant, we also show that the perturbation of OB-OB contacts significantly impairs the stability of SSB tetramers and results in thermally induced protein aggregation, underscoring the importance of multivalence brought about by stereospecific contacts. Our data point to adaptive fine-tuning of SSB interactions to physiological condensation and demonstrate that SSB represents a versatile system for selective engineering of condensation-driving interactions between globular and disordered regions.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 4","pages":"e70109"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visualizing and analyzing 3D biomolecular structures using Mol* at RCSB.org: Influenza A H5N1 virus proteome case study.","authors":"Sebastian Bittrich, Alexander S Rose, David Sehnal, Jose M Duarte, Yana Rose, Joan Segura, Dennis W Piehl, Brinda Vallat, Chenghua Shao, Charmi Bhikadiya, Jesse Liang, Mark Ma, David S Goodsell, Stephen K Burley, Shuchismita Dutta","doi":"10.1002/pro.70093","DOIUrl":"10.1002/pro.70093","url":null,"abstract":"<p><p>The easiest and often most useful way to work with experimentally determined or computationally predicted structures of biomolecules is by viewing their three-dimensional (3D) shapes using a molecular visualization tool. Mol* was collaboratively developed by RCSB Protein Data Bank (RCSB PDB, RCSB.org) and Protein Data Bank in Europe (PDBe, PDBe.org) as an open-source, web-based, 3D visualization software suite for examination and analyses of biostructures. It is capable of displaying atomic coordinates and related experimental data of biomolecular structures together with a variety of annotations, facilitating basic and applied research, training, education, and information dissemination. Across RCSB.org, the RCSB PDB research-focused web portal, Mol* has been implemented to support single-mouse-click atomic-level visualization of biomolecules (e.g., proteins, nucleic acids, carbohydrates) with bound cofactors, small-molecule ligands, ions, water molecules, or other macromolecules. RCSB.org Mol* can seamlessly display 3D structures from various sources, allowing structure interrogation, superimposition, and comparison. Using influenza A H5N1 virus as a topical case study of an important pathogen, we exemplify how Mol* has been embedded within various RCSB.org tools-allowing users to view polymer sequence and structure-based annotations integrated from trusted bioinformatics data resources, assess patterns and trends in groups of structures, and view structures of any size and compositional complexity. In addition to being linked to every experimentally determined biostructure and Computed Structure Model made available at RCSB.org, Standalone Mol* is freely available for visualizing any atomic-level or multi-scale biostructure at rcsb.org/3d-view.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 4","pages":"e70093"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel protein for bioremediation of gadolinium waste.","authors":"Harvey D Lee, Connor J Grady, Katie Krell, Cooper Strebeck, Aimen Al-Hilfi, Brianna Ricker, Melanie Linn, Nicole Y Xin, Nathan M Good, N Cecilia Martinez-Gomez, Assaf A Gilad","doi":"10.1002/pro.70101","DOIUrl":"10.1002/pro.70101","url":null,"abstract":"<p><p>Several hundreds of tons of gadolinium-based contrast agents (GBCAs) are being dumped into the environment every year. Although macrocyclic GBCAs exhibit superior stability compared to their linear counterparts, we have found that the structural integrity of chelates is susceptible to ultraviolet light, regardless of configuration. In this study, we present a synthetic protein termed GLamouR that binds and reports gadolinium in an intensiometric manner. We then explore the extraction of gadolinium from MRI patient urine as a preventative measure for gadolinium pollution and investigate the viability of employing cost-effective bioremediation techniques for treating contaminated water bodies. Based on promising results, we anticipate proteins such as GLamouR can be used for detecting and mining rare earth elements beyond gadolinium and hope to expand the biological toolbox for such applications.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 4","pages":"e70101"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solution structure of the Z0 domain from transcription repressor BCL11A sheds light on the sequence properties of protein-binding zinc fingers.","authors":"Rilee E Harris, Richard D Whitehead, Andrei T Alexandrescu","doi":"10.1002/pro.70097","DOIUrl":"10.1002/pro.70097","url":null,"abstract":"<p><p>The transcription repressor BCL11A governs the switch from fetal to adult hemoglobin during development. By targeting BCL11A, fetal hemoglobin expression can be de-repressed to substitute for defective adult hemoglobin in inherited diseases including beta-thalassemia and sickle-cell anemia. BCL11A has six CCHH-type zinc fingers, of which domains 4-6 are necessary and sufficient for dsDNA binding. Here, we focus on a putative ZNF at the N-terminus of BCL11A (residues 46-72), Z0, thought to modulate oligomerization of the transcription repressor. Using NMR and CD spectroscopy at low concentrations that favor the monomer, Z0 is shown to be a thermostable CCHC zinc finger with a pM dissociation constant for zinc. The NMR structure of Z0 has a prototypical beta-beta-alpha fold, with a hydrophobic knob comprising about half the structure. The unusual proportion of hydrophobic residues in Z0 led us to investigate if this is a more general feature of zinc fingers that do not bind dsDNA. We used the ZF and WebLogo servers to examine sequences of zinc fingers with demonstrated DNA-binding function, non-DNA-binders, and the CCHC-type family of protein-binders. DNA-binders are distinguished by contiguous stretches of high-scoring zinc fingers. Non-DNA-binders show a depletion of polar residues at the positions expected to contact nucleotides and increased sequence divergence, making these domains more likely to be annotated as atypical, degenerate, or to be missed as zinc fingers. We anticipate these sequence patterns will help distinguish DNA-binders from non-binders, an open problem in the functional understanding of zinc-finger motifs.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 4","pages":"e70097"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crowding beyond excluded volume: A tale of two dimers.","authors":"Gil I Olgenblum, Claire J Stewart, Thomas W Redvanly, Owen M Young, Francis Lauzier, Sophia Hazlett, Shikun Wang, David A Rockcliffe, Stuart Parnham, Gary J Pielak, Daniel Harries","doi":"10.1002/pro.70062","DOIUrl":"10.1002/pro.70062","url":null,"abstract":"<p><p>Protein-protein interactions are modulated by their environment. High macromolecular solute concentrations crowd proteins and shift equilibria between protein monomers and their assemblies. We aim to understand the mechanism of crowding by elucidating the molecular-level interactions that determine dimer stability. Using ¹⁹F-NMR spectroscopy, we studied the effects of various polyethylene glycols (PEGs) on the equilibrium thermodynamics of two protein complexes: a side-by-side and a domain-swap dimer. Analysis using our mean-field crowding model shows that, contrary to classic crowding theories, PEGs destabilize both dimers through enthalpic interactions between PEG and the monomers. The enthalpic destabilization becomes more dominant with increasing PEG concentration because the reduction in PEG mesh size with concentration diminishes the stabilizing effect of excluded volume interactions. Additionally, the partially folded domain-swap monomers fold in the presence of PEG, contributing to dimer stabilization at low PEG concentrations. Our results reveal that polymers crowd protein complexes through multiple conjoined mechanisms, impacting both their stability and oligomeric state.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 4","pages":"e70062"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural insights into the fusion of annexin A5 and fluorescent proteins generating hundredfold differentiated binding affinities to phosphatidylserine.","authors":"Mengyue Gao, Wei Tang, Shihui Wang, Yunke Wang, Minjin Hu, Zichun Hua","doi":"10.1002/pro.70086","DOIUrl":"10.1002/pro.70086","url":null,"abstract":"<p><p>Fluorescent proteins (FPs) are an indispensable part of modern biology. Numerous studies utilize FPs for protein labeling and cell tracking purposes. They are commonly fused with proteins to aid in their visualization. It is generally assumed that these FP tags have minimal impact on the properties of the fusion proteins. Do the FP types affect the function and characteristics of target proteins on earth? So far, there is no definite answer. Fluorescent annexin A5 (AnxA5) has been extensively employed as apoptosis probes. However, except for chemically labeled AnxA5, there are few developed FP-based AnxA5 probes. Therefore, it is essential to screen out suitable FPs for developing high-affinity AnxA5 probes. Here, various fusion proteins (AnxA5-FPs) were developed. The fusion of AnxA5 did not change the chromophore environments of FPs, while the fusion of FPs led to over a 100-fold difference in AnxA5's affinity for phosphatidylserine (PS). We found that polymeric AnxA5-FPs had higher PS-affinity. Remarkably, although the structures of FPs were similar, they fused with AnxA5 in different modes, generating fusion proteins with different spatial conformations. The difference in conformation resulted in variations in the PS-binding pattern of AnxA5, leading to differing levels of PS-affinity. More importantly, we found five high-affinity (Kd > 10^-7 M) FP-based AnxA5 probes with different excitation wavelengths. Together, these observations suggested that differences in the fusion modes of AnxA5 and FPs provided a robust mechanism for modulating PS-affinity of AnxA5. We anticipate that our findings can provide a guideline to develop highly sensitive AnxA5 probes.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 4","pages":"e70086"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanism of Mad2 conformational conversion promoted by the Mad2-interaction motif of Cdc20.","authors":"Conny W H Yu, Elyse S Fischer, Joe G Greener, Jing Yang, Ziguo Zhang, Stefan M V Freund, David Barford","doi":"10.1002/pro.70099","DOIUrl":"10.1002/pro.70099","url":null,"abstract":"<p><p>During mitosis, unattached kinetochores trigger the spindle assembly checkpoint by promoting the assembly of the mitotic checkpoint complex, a heterotetramer comprising Mad2, Cdc20, BubR1, and Bub3. Critical to this process is the kinetochore-mediated catalysis of an intrinsically slow conformational conversion of Mad2 from an open (O-Mad2) inactive state to a closed (C-Mad2) active state bound to Cdc20. These Mad2 conformational changes involve substantial remodeling of the N-terminal β1 strand and C-terminal β7/β8 hairpin. In vitro, the Mad2-interaction motif (MIM) of Cdc20 (Cdc20^MIM) triggers the rapid conversion of O-Mad2 to C-Mad2, effectively removing the kinetic barrier for MCC assembly. How Cdc20^MIM directly induces Mad2 conversion remains unclear. In this study, we demonstrate that the Cdc20^MIM-binding site is inaccessible in O-Mad2. Time-resolved NMR and molecular dynamics simulations show how Mad2 conversion involves sequential conformational changes of flexible structural elements in O-Mad2, orchestrated by Cdc20^MIM. Conversion is initiated by the β7/β8 hairpin of O-Mad2 transiently unfolding to expose a nascent Cdc20^MIM-binding site. Engagement of Cdc20^MIM to this site promotes the release of the β1 strand. We propose that initial conformational changes of the β7/β8 hairpin allow binding of Cdc20^MIM to a transient intermediate state of Mad2, thereby lowering the kinetic barrier to Mad2 conversion.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 4","pages":"e70099"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solid-state NMR protocols for unveiling dynamics and (drug) interactions of membrane-bound proteins.","authors":"Alessia Lasorsa, Patrick C A van der Wel","doi":"10.1002/pro.70102","DOIUrl":"10.1002/pro.70102","url":null,"abstract":"<p><p>Magic angle spinning solid-state NMR (MAS ssNMR) is a versatile tool for studying the structure and dynamics of membrane proteins, as well as their interactions with ligands and drugs. Its power lies in the ability to provide atomic-level information on samples under physiological-like conditions. Moreover, it can illuminate dynamics across a wide range of timescales with great relevance to membrane protein function and dysfunction. In this protocol paper, we highlight key aspects of sample preparation, data acquisition, and interpretation, based on our own experience and the broader literature. We discuss key protocol steps along with important considerations for sample preparation and parameters for ssNMR measurements, with reference to the special requirements of membrane-based samples. Such samples display physiologically relevant dynamics across different motional regimes that can be probed by NMR but also can interfere with certain NMR measurements. We guide the reader through the whole process from sample preparation to complex NMR characterization techniques. Throughout the report, we refer back to examples from our own prior work on the interactions between cytochrome c and cardiolipin-containing membranes, with a discussion of the lipid dependence and interactions with a peroxidase-activity inhibitor. We conclude with a short discussion of alternative and new methods that are further boosting the power and versatility of ssNMR as a tool to study membrane-bound proteins and their ligands or drug interactions.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 4","pages":"e70102"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of non-native species formed during fibrillization of the myocilin olfactomedin domain.","authors":"Hailee F Scelsi, Emily G S Close, Dustin J E Huard, Elijah Dunn, Nebojša Bogdanović, Sonali H W Mudiyanselage, Arshay Grant, Scott M Stagg, Ingeborg Schmidt-Krey, Wade D Van Horn, Raquel L Lieberman","doi":"10.1002/pro.70063","DOIUrl":"10.1002/pro.70063","url":null,"abstract":"<p><p>Glaucoma is a group of neurodegenerative diseases that together are the leading cause of irreversible blindness worldwide. Myocilin-associated glaucoma is an inherited form of this disease, caused by intracellular aggregation of misfolded mutant myocilin. In vitro, the myocilin C-terminal olfactomedin domain (OLF), the relevant domain for glaucoma pathogenesis, can be driven to form amyloid-like fibrils under mild conditions. Here we characterize a species present during in vitro fibrillization. Purified OLF was subjected to fibrillization at concentrations required for downstream electron microscopy imaging and NMR spectroscopy. Additional biophysical techniques, including analytical ultracentrifugation and X-ray crystallography, were employed to further characterize the multicomponent mixture. Negative stain transmission electron microscopy (TEM) shows a non-native species reminiscent of known prefibrillar oligomers from other amyloid systems, NMR indicates a minor population of partially misfolded species is present in solution, and cryo-EM imaging shows two-dimensional protein arrays. The predominant soluble species remaining in solution after the fibril reaction is natively folded, as evidenced by X-ray crystallography. In summary, after incubating OLF under fibrillization-promoting conditions, there is a heterogeneous mixture consisting of soluble folded protein, mature amyloid-like fibrils, and partially misfolded intermediate species that at present belie additional molecular detail. The characterization of OLF fibrillar species illustrates the challenges associated with developing a comprehensive understanding of the fibrillization process for large, non-model amyloidogenic proteins.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 4","pages":"e70063"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11912428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}