M Mubinur Rahman, Ramita Sulu, Bukunmi Adediran, Hongmin Tu, Antti M Salo, Sudarshan Murthy, Johanna Myllyharju, Rik K Wierenga, M Kristian Koski
{"title":"Binding Differences of the Peptide-Substrate-Binding Domain of Collagen Prolyl 4-Hydroxylases I and II for Proline- and Hydroxyproline-Rich Peptides.","authors":"M Mubinur Rahman, Ramita Sulu, Bukunmi Adediran, Hongmin Tu, Antti M Salo, Sudarshan Murthy, Johanna Myllyharju, Rik K Wierenga, M Kristian Koski","doi":"10.1002/prot.26839","DOIUrl":"10.1002/prot.26839","url":null,"abstract":"<p><p>Collagen prolyl 4-hydroxylase (C-P4H) catalyzes the 4-hydroxylation of Y-prolines of the XYG-repeat of procollagen. C-P4Hs are tetrameric α<sub>2</sub>β<sub>2</sub> enzymes. The α-subunit provides the N-terminal dimerization domain, the middle peptide-substrate-binding (PSB) domain, and the C-terminal catalytic (CAT) domain. There are three isoforms of the α-subunit, complexed with a β-subunit that is protein disulfide isomerase, forming C-P4H I-III. The PSB domain of the α-subunit binds proline-rich peptides, but its function with respect to the prolyl hydroxylation mechanism is unknown. An extended mode of binding of proline-rich peptides (PPII, polyproline type-II, conformation) to the PSB-I domain has previously been reported for the PPG-PPG-PPG and P9 peptides. Crystal structures now show that peptides with the motif PxGP (PPG-PRG-PPG, PPG-PAG-PPG) (where x, at Y-position 5, is not a proline) bind to the PSB-I domain differently, more deeply, in the peptide-binding groove. The latter mode of binding has previously been reported for structures of the PSB-II domain complexed with these PxGP-peptides. In addition, it is shown here by crystallographic binding studies that the POG-PAG-POG peptide (with 4-hydroxyprolines at Y-positions 2 and 8) also adopts the PxGP mode of binding to PSB-I as well as to PSB-II. Calorimetric binding studies show that the affinities of these peptides are lower for PSB-I than for PSB-II, with, respectively, K<sub>D</sub> values of about 70 μM for PSB-I and 20 μM for PSB-II. The importance of these results for understanding the reaction mechanism of C-P4H, in particular concerning the function of the PSB domain, is discussed.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1732-1746"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Using AlphaFold and Symmetrical Docking to Predict Protein-Protein Interactions for Exploring Potential Crystallization Conditions.","authors":"Kuan-Ju Liao, Yuh-Ju Sun","doi":"10.1002/prot.26844","DOIUrl":"10.1002/prot.26844","url":null,"abstract":"<p><p>Protein crystallization remains a major bottleneck in X-ray crystallography due to difficulties in achieving favorable molecular arrangements within the crystal lattice. While protein-protein interactions at molecular packing interfaces are crucial for determining crystallization conditions, methods for predicting crystal packing interfaces and systematically exploring crystallization conditions remain limited. In this study, we present MASCL (Molecular Assembly Simulation in Crystal Lattice), a novel approach that integrates AlphaFold with symmetrical docking to simulate crystal packing. To evaluate packing quality, we introduced PackQ, a stringent metric based on the DockQ framework, where models with scores above 0.36 are considered successful. In benchmark tests on P4<sub>1</sub>2<sub>1</sub>2 and P4<sub>3</sub>2<sub>1</sub>2 space groups, MASCL successfully predicted packing interfaces for 26.8% and 30.1% of targets within the top 100 models. When focusing on models with successfully predicted initial crystallographic dimeric assemblies (DockQ ≥ 0.23), success rates improved to 57.9% and 39.8% within the top 25 models, respectively. Additionally, we developed AAI-PatchBag, a patch-based method using physicochemical descriptors to assess molecular interface similarity. Compared to conventional condition-searching strategies like sequence alignment, structure superposition, and shape comparison, AAI-PatchBag reduced the number of trials required to identify potential crystallization conditions. Applied to lysozyme crystallization, AAI-PatchBag efficiently identified conditions yielding crystals with the desired packing. Overall, MASCL and AAI-PatchBag advance the prediction of protein-protein interactions within the crystal lattice and facilitate the identification of potential crystallization conditions through molecular packing interface similarity, contributing to a deeper understanding of protein crystallization.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1747-1766"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Durga Geetha, B A Aysha Hameeda, Deepthi Jose, Nishamol Kuriakose, Tom Skaria
{"title":"Novel Insights Into the Dynamic Conformational Transitions and Active Site Plasticity of Human Immunoregulatory Cathepsin S.","authors":"Durga Geetha, B A Aysha Hameeda, Deepthi Jose, Nishamol Kuriakose, Tom Skaria","doi":"10.1002/prot.26845","DOIUrl":"10.1002/prot.26845","url":null,"abstract":"<p><p>Cathepsin S (CatS), a cysteine protease, catalyzes the cleavage of immunoregulatory peptides and mediates tissue destruction in autoimmune and inflammatory diseases. Plasticity of its ligand binding site and mechanisms of dynamic transitions between different conformational states are critical in drug discovery; however, knowledge of its entire conformational landscape and transition mechanisms remains incomplete. Therefore, we investigated the atomic-level interactions between active site cleft residues that contribute to its structural and functional plasticity. Here, we show that the hinge movement of side chains of Phe211, Phe70, and Tyr118, followed by side chain reorientation of active site residues and inter-residue interactions, results in open or closed conformations, contributing to the plasticity of the S2 binding affinity hotspot pocket of CatS. Hinge movements of Phe211, Phe70, and Tyr118 regulate the space available in the S2 pocket, with Phe70 acting as a key regulator, thereby affecting small molecule binding in the active site cleft. Further, the non-covalent interactions between active site residues during transitions between open and closed states lead to the formation of three distinct, dynamic, semi-closed substates. The transition to the closed state can be blocked by a ligand that sterically hinders the hinge movement of Phe70 or Phe211. The cooperative, organized side chain rotation of Phe211, Phe70, and Tyr118, and subsequent emergence of non-covalent interactions between the active site residues can influence the accommodation of ligands and their specificity. These novel findings might further aid the design of selective small molecule drugs targeting specific conformational states of the immunoregulatory and inflammatory/autoimmune disease target human CatS.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1805-1818"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jimin Pei, R Dustin Schaeffer, Qian Cong, Nick V Grishin
{"title":"Case Studies of Orphan Domain Reclassification in ECOD by Expert Curation.","authors":"Jimin Pei, R Dustin Schaeffer, Qian Cong, Nick V Grishin","doi":"10.1002/prot.26840","DOIUrl":"10.1002/prot.26840","url":null,"abstract":"<p><p>Homology-based protein domain classification is a powerful tool for gaining biological insights into protein function. This classification process has been significantly enhanced by the availability of experimental structures and high-accuracy structural models generated by advanced tools such as AlphaFold. Our Evolutionary Classification of protein Domains (ECOD) database provides a continuously updated and refined domain classification system. Isolated (\"orphan\") protein domain families, which have a limited distribution in the protein universe, present a unique challenge in this classification process. These families lack clear or identifiable evolutionary relationships with other sequence families. While some isolated domain families may have emerged through de novo evolution, others potentially share common evolutionary origins with existing domain families but represent difficult cases for traditional classification methods. In this study, we conducted a manual analysis of a set of isolated families of small domains in ECOD. By exploring sequence, structural, and functional evidence, we uncovered distant members and likely homologous relationships between different isolated domain families that were previously unrecognized. Our analysis provides valuable insights into the evolution of isolated domain families and has led to improved classification within ECOD. This work enhances our understanding of protein evolution and underscores the importance of continuous refinement in domain classification systems as new data and analytical methods become available.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1780-1789"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aanchal Mishra, Stéphane Goffinont, Franck Coste, El Hadji Cisse, Lucija Mance, Bertrand Castaing, Marcin J Suskiewicz
{"title":"Fusion Protein-Assisted Crystallization of Human SUMO1.","authors":"Aanchal Mishra, Stéphane Goffinont, Franck Coste, El Hadji Cisse, Lucija Mance, Bertrand Castaing, Marcin J Suskiewicz","doi":"10.1002/prot.26838","DOIUrl":"10.1002/prot.26838","url":null,"abstract":"<p><p>In this study, we employed a fusion protein-assisted approach to crystallize human SUMO1, an essential covalent protein modifier that also interacts noncovalently with specific linear protein motifs called SUMO-interacting motifs (SIMs). SUMO1 has been crystallized previously as part of various complexes but never in isolation. Our strategy involved fusing a variant of a known crystallization facilitator, the TELSAM domain, upstream of the folded part of the SUMO1 protein (residues 18-97). Following a simple purification strategy, we obtained a 2.05-Å crystal structure of apo TELSAM-SUMO1, with three distinct SUMO1 chains per asymmetric unit, two of which have an accessible pocket for binding to a SIM. The crystal structure is composed of the expected left-handed helical filaments formed by TELSAM domains, with protruding SUMO1 molecules mediating connections within and between these filaments to stabilize a three-dimensional lattice. Since the TELSAM fusion does not affect the SUMO:SIM interaction, as confirmed in solution, our construct may potentially be used to structurally characterize complexes formed between SUMO and SIM-containing peptides. Neither does the TELSAM fusion interfere with the attachment of SUMO1 to substrates, potentially allowing for the creation of SUMOylated protein forms with improved crystallizability. The study represents a novel application of TELSAM-assisted crystallization to a small protein of major biological relevance.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1767-1779"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"De Novo Design of Highly Stable Binders Targeting Dihydrofolate Reductase in Klebsiella pneumoniae.","authors":"Ihteshamul Haq, Faheem Anwar, Yigang Tong","doi":"10.1002/prot.26835","DOIUrl":"10.1002/prot.26835","url":null,"abstract":"<p><p>The study aims to design novel therapeutic inhibitors targeting the DHFR protein of Klebsiella pneumoniae. However, challenges like bacterial resistance to peptides and the limitations of computational models in predicting in vivo behavior must be addressed to refine the design process and improve therapeutic efficacy. This study employed deep learning-based bioinformatics techniques to tackle these issues. The study involved retrieving DHFR protein sequences from Klebsiella strains, aligning them to identify conserved regions, and using deep learning models (OmegaFold, ProteinMPNN) to design de novo inhibitors. Cell-penetrating peptide (CPP) motifs were added to enhance delivery, followed by allergenicity and thermal stability assessments. Molecular docking and dynamics simulations evaluated the binding affinity and stability of the inhibitors with DHFR. A conserved 60-residue region was identified, and 60 de novo binders were generated, resulting in 7200 sequences. After allergenicity prediction and stability testing, 10 sequences with melting points near 70°C were shortlisted. Strong binding affinities were observed, especially for complexes 4OR7-1787 and 4OR7-1811, which remained stable in molecular dynamics simulations, indicating their potential as therapeutic agents. This study designed stable de novo peptides with cell-penetrating properties and strong binding affinity to DHFR. Future steps include in vitro validation to assess their effectiveness in inhibiting DHFR, followed by in vivo studies to evaluate their therapeutic potential and stability. These peptides offer a promising strategy against Klebsiella pneumoniae infections, providing potential alternatives to current antibiotics. Experimental validation will be key to assessing their clinical relevance.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1675-1687"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shriyansh Srivastava, Vishnu A M, Rakesh Thakur, Ashutosh Srivastava
{"title":"REV-ERBβ Binding Pocket Dynamics With Implications for Rational Design of Small Molecule Modulators.","authors":"Shriyansh Srivastava, Vishnu A M, Rakesh Thakur, Ashutosh Srivastava","doi":"10.1002/prot.26841","DOIUrl":"10.1002/prot.26841","url":null,"abstract":"<p><p>REV-ERBβ is a nuclear receptor (NR) with heme as an endogenous ligand that regulates its transcriptional activity. With a key role in cellular functions such as glucose metabolism, immune response, and dysregulation in pathologies such as Type-2 diabetes mellitus and obesity, small molecule agonists and antagonists targeting REV-ERBs have been discovered. However, due to a lack of crystal structures in complex with these compounds, the structural and dynamical basis of these activities still remains elusive and hinders the rational design of molecules targeting REV-ERB. Using molecular dynamics simulations and docking studies, we have characterized the dynamics of REV-ERBβ ligand-binding domain (LBD) in different conformational states. The presence of heme in the binding pocket within LBD was found to dampen its dynamics as well as nuclear co-repressor (NCoR) peptide binding. We further show that the binding of the antagonist destabilizes the NCoR peptide binding to LBD mediated by loss of interactions with residues at the NCoR-REV-ERBβ interface. These findings could be utilized to design molecular scaffolds with better activity and selectivity against REV-ERBβ.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1790-1804"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DeepUSPS: Deep Learning-Empowered Unconstrained-Structural Protein Sequence Design.","authors":"Zhichong Ma, Jiawen Yang","doi":"10.1002/prot.26847","DOIUrl":"10.1002/prot.26847","url":null,"abstract":"<p><p>Currently, the unconstrained-structural protein sequence design models suffer from low optimization efficiency, and their generated proteins exhibit significant similarities to natural proteins and low thermal stability. To address these challenges, we propose the Deep Learning-Empowered Unconstrained-Structural Protein Sequence Design (DeepUSPS) model. To effectively address the inadequate thermal stability problem, we employ the innovative Inverted Dense Residual Network (IDRNet). To mitigate the designed proteins similarity issue, the Sequence-Pairwise Features Extraction Synthetic Network (SPFESN) is constructed. Furthermore, we introduce the Warm Restart AngularGrad (WRA) optimizer to optimize the 3D Position-Specific Scoring Matrix (3Dpssm) for unconstrained-structural protein sequence, only involving 2100 iterations (140.36 min) updates to generate idealization (IDE) protein sequences. We obtained a total of 1000 IDE protein sequences. Then we utilized in silico experiments to evaluate them, including similarity, clarity and iterations, thermal stability, spatial distribution of similarity, and predicted local-distance difference test (pLDDT) confidence assessment. Notably, the mean lg(E-value) for IDE protein sequences reached -0.051, the mean TM-score for IDE protein structures reached 0.594, the iterations only need 2100, and the mean Tm (melting point) for thermal stability reached 74.78°C. The average pLDDT value for 3D structures reached 76. Additionally, the IDE proteins' 3D structures exhibit diverse types. These in silico results conclusively demonstrate the superior performance of DeepUSPS compared with Hallucinate.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1819-1836"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L B Arend, D S Lima, M G S Costa, F K Ricachenevsky, H Verli
{"title":"Molecular Basis for Vacuolar Iron Transport by OsVIT2, a Target for Iron Biofortification in Rice.","authors":"L B Arend, D S Lima, M G S Costa, F K Ricachenevsky, H Verli","doi":"10.1002/prot.26843","DOIUrl":"10.1002/prot.26843","url":null,"abstract":"<p><p>Iron deficiency is the prevalent and most widespread nutritional shortfall for humans, affecting over 30% of the global population and leading to anemia, particularly among preschool-aged children and pregnant women in developing countries. Simultaneously, while half of the world's population depends on rice (Oryza sativa L.) as a staple food, this cereal does not provide a sufficient amount of that micronutrient to meet these people's nutritional needs: even when iron is readily available in the soil, it does not accumulate in the consumed portion of the grain, namely, the starchy endosperm, being instead retained in the aleurone layer, in the pericarp and in the embryo. In this context, the present work applies computational biology tools-such as normal mode analysis and molecular dynamics simulations-to elucidate the behavior and transport mechanism of the Vacuolar Iron Transporter 2 (OsVIT2), a central protein for iron homeostasis in rice, with the objective of laying the foundations for future OsVIT2 engineering projects that could be articulated with ongoing efforts to promote iron biofortification in rice. We shed light on the interplay between protonation state, configuration and hydration of OsVIT2's pore; on the mechanics of its opening and on the ever-shifting hydrogen bond network contained within it. We also explore the potential contribution of the \"flexible arms\" to the iron-capturing function performed by the cytoplasmic domain.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1717-1731"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefan Loonen, Lina van Steenis, Marianne Bauer, Nikolina Šoštarić
{"title":"Phosphorylation Changes SARS-CoV-2 Nucleocapsid Protein's Structural Dynamics and Its Interaction With RNA.","authors":"Stefan Loonen, Lina van Steenis, Marianne Bauer, Nikolina Šoštarić","doi":"10.1002/prot.26842","DOIUrl":"10.1002/prot.26842","url":null,"abstract":"<p><p>The SARS-CoV-2 nucleocapsid protein, or N-protein, is a structural protein that plays an important role in the SARS-CoV-2 life cycle. The N-protein takes part in the regulation of viral RNA replication and drives highly specific packaging of full-length genomic RNA prior to virion formation. One regulatory mechanism that is proposed to drive the switch between these two operating modes is the phosphorylation state of the N-protein. Here, we assess the dynamic behavior of non-phosphorylated and phosphorylated versions of the N-protein homodimer through atomistic molecular dynamics simulations. We show that the introduction of phosphorylation yields a more dynamic protein structure and decreases the binding affinity between the N-protein and RNA. Furthermore, we find that secondary structure is essential for the preferential binding of particular RNA elements from the 5' UTR of the viral genome to the N-terminal domain of the N-protein. Altogether, we provide detailed molecular insights into N-protein dynamics, N-protein:RNA interactions, and phosphorylation. Our results corroborate the hypothesis that phosphorylation of the N-protein serves as a regulatory mechanism that determines N-protein function.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1701-1716"},"PeriodicalIF":2.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}