Protein Science最新文献

{"title":"Combining computational modeling and experimental library screening to affinity-mature VEEV-neutralizing antibody F5.","authors":"Christopher A Sumner, Jennifer L Schwedler, Katherine Maia McCoy, Jack Holland, Valerie Duva, Daniel Gelperin, Valeria Busygina, Maxwell A Stefan, Daniella V Martinez, Miranda A Juarros, Ashlee M Phillips, Dina R Weilhammer, Gevorg Grigoryan, Michael S Kent, Brooke N Harmon","doi":"10.1002/pro.70043","DOIUrl":"10.1002/pro.70043","url":null,"abstract":"<p><p>Engineered monoclonal antibodies have proven to be highly effective therapeutics in recent viral outbreaks. However, despite technical advancements, an ability to rapidly adapt or increase antibody affinity and by extension, therapeutic efficacy, has yet to be fully realized. We endeavored to stand-up such a pipeline using molecular modeling combined with experimental library screening to increase the affinity of F5, a monoclonal antibody with potent neutralizing activity against Venezuelan Equine Encephalitis Virus (VEEV), to recombinant VEEV (IAB) E1E2 antigen. We modeled the F5/E1E2 binding interface and generated predictions for mutations to improve binding using a Rosetta-based approach and dTERMen, an informatics approach. The modeling was complicated by the fact that a high-resolution structure of F5 is not available and the H3 loop of F5 exceeds the length for which current modeling approaches can determine a unique structure. A subset of the predicted mutations from both methods were incorporated into a phage display library of scFvs. This library and a library generated by error-prone PCR were screened for binding affinity to the recombinant antigen. Results from the screens identified favorable mutations which were incorporated into 12 human-IgG1 variants. The best variant, containing eight mutations, improved KD from 0.63 nM (parental) to 0.01 nM. While this did not improve neutralization or therapeutic potency of F5 against IAB, it did increase cross-reactivity to other closely related VEEV epizootic and enzootic strains, demonstrating the potential of this method to rapidly adapt existing therapeutics to emerging viral strains.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 2","pages":"e70043"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010383","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":"Computational and experimental mapping of the allosteric network of two manganese ABC transporters.","authors":"Ozge Duman, Anastasiya Kuznetsova, Nurit Livnat Levanon, Moti Grupper, Akarun Ayca Ersoy, Burcin Acar, Amit Kessel, Nir Ben-Tal, Oded Lewinson, Turkan Haliloglu","doi":"10.1002/pro.70039","DOIUrl":"10.1002/pro.70039","url":null,"abstract":"<p><p>Transition metals (e.g., Fe^2/3+, Zn²⁺, Mn²⁺) are essential enzymatic cofactors in all organisms. Their environmental scarcity led to the evolution of high-affinity uptake systems. Our research focuses on two bacterial manganese ABC importers, Streptococcus pneumoniae PsaBC and Bacillus anthracis MntBC, both critical for virulence. Both importers share a similar homodimeric structure, where each protomer comprises a transmembrane domain (TMD) linked to a cytoplasmic nucleotide-binding domain (NBD). Due to their size and slow turnover rates, the utility of conventional molecular simulation approaches to reveal functional dynamics is limited. Thus, we employed a novel, computationally efficient method integrating Gaussian Network Models (GNM) with information theory Transfer Entropy (TE) calculations. Our calculations are in remarkable agreement with previous functional studies. Furthermore, based on the calculations, we generated 10 point-mutations and experimentally tested their effects, finding excellent concordance between computational predictions and experimental results. We identified \"allosteric hotspots\" in both transporters, in the transmembrane translocation pathway, at the coupling helices linking the TMDs and NBDs, and in the ATP binding sites. In both PsaBC and MntBC, we observed bi-directional information flow between the two TMDs, with minimal allosteric transmission to the NBDs. Conversely, the NBDs exhibited almost no NBD-NBD allosteric crosstalk but showed pronounced information flow from the NBD of one protomer towards the TMD of the other protomer. This unique allosteric \"footprint\" distinguishes ABC importers of transition metals from other members of the ABC transporter superfamily establishing them as a distinct functional class. This study offers the first comprehensive insight into the conformational dynamics of these vital virulence determinants, providing potential avenues for developing urgently needed novel antibacterial agents.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 2","pages":"e70039"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067612","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":"Citrullination at the N-terminal region of MDM2 by the PADI4 enzyme.","authors":"José L Neira, Bruno Rizzuti, Martina Palomino-Schätzlein, Virginia Rejas, Olga Abian, Adrian Velazquez-Campoy","doi":"10.1002/pro.70033","DOIUrl":"10.1002/pro.70033","url":null,"abstract":"<p><p>PADI4 is one of the human isoforms of a family of enzymes involved in the conversion of arginine to citrulline. MDM2 is an E3 ubiquitin ligase that is critical for degradation of the tumor suppressor gene p53. We have previously shown that there is an interaction between MDM2 and PADI4 in cellulo, and that such interaction occurs through the N-terminal region of MDM2, N-MDM2, and in particular through residues Thr26, Val28, Phe91, and Lys98. Here, by using a \"divide-and-conquer\" approach, we have designed and synthesized peptides comprising these two polypeptide stretches (residues Ala21-Lys36, and Lys94-Val108), either in the wild-type species or in their citrullinated versions. Some of the citrullinated peptides were aggregation-prone, as suggested by DOSY-NMR experiments, but the wild-type versions of both fragments were monomeric in solution. We found out that wild-type and modified peptides were disordered in all cases, as also tested by far-UV circular dichroism (CD), and citrullination mainly affected the NMR chemical shifts of adjacent residues. Isothermal titration calorimetry (ITC) in the absence and presence of GSK484, an enzymatic PADI4 inhibitor, indicated that this compound blocked binding of the peptides to the enzyme. Binding to the active site of the N-MDM2 fragments was also confirmed by in silico experiments. The affinities of PADI4 for the wild-type peptides were more favorable than those of the corresponding citrullinated ones, but all measured values were within the micromolar range, indicating that there were no major variations in the thermodynamics of binding due to sequence effects. The kinetic dissociation rates, k_off, measured by biolayer interferometry (BLI), were always one-order of magnitude faster for the citrullinated peptides than for the wild-type ones. Taken together, all these findings indicate that MDM2 is a substrate for PADI4 and is prone to citrullination in the identified (and specific) positions of its N-terminal region.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 2","pages":"e70033"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010378","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":"Hijacking of plasminogen by dengue virus: The kringle-4 and -5 domains of plasminogen binds synergistically to the domain I of envelope protein.","authors":"Yee Jun Yuen, Thekkoot Sabitha, Lim Jian Li, Varsha Ashok Walvekar, Karthik Ramesh, R Manjunatha Kini, J Sivaraman, Yu Keung Mok","doi":"10.1002/pro.70035","DOIUrl":"10.1002/pro.70035","url":null,"abstract":"<p><p>Dengue fever is a serious health issue, particularly in tropical countries like Singapore. We have previously found that dengue virus (DENV) recruits human plasmin in blood meal to enhance the permeability of the mosquito midgut for infection. Here, using biolayer interferometry, we found that neither kringle-4 nor kringle-5 plasmin domains alone binds well to dengue virus. However, the domains together lead to a synergistic effect, with both kringle-4 and -5 domains required and sufficient for binding. Site-directed mutagenesis experiments showed that the N-terminal and C-terminal aspartic acid residues in the \"DXD\" acidic motifs of the kringle-4 and -5 domains likely have different roles when engaged with DENV. Hydrogen deuterium exchange mass spectrometry experiments on the plasmin:DENV complex led to the identification of two Lys-containing regions on domain I of the E-protein of DENV that are buried by plasmin and could be potential plasmin binding sites. These findings contradict with published literature that domain III of the DENV E-protein interacts with the kringle-1-3 domains of plasmin. We provide a plausible explanation for the observed discrepancies.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 2","pages":"e70035"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010406","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":"Ca^XML: Chemistry-informed machine learning explains mutual changes between protein conformations and calcium ions in calcium-binding proteins using structural and topological features.","authors":"Pengzhi Zhang, Jules Nde, Yossi Eliaz, Nathaniel Jennings, Piotr Cieplak, Margaret S Cheung","doi":"10.1002/pro.70023","DOIUrl":"10.1002/pro.70023","url":null,"abstract":"<p><p>Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes. However, it is unclear whether the limited experimental data available can be effectively used to train models to accurately predict the charges of calcium-binding protein variants. Here, we developed a chemistry-informed, machine-learning algorithm that implements a game theoretic approach to explain the output of a machine-learning model without the prerequisite of an excessively large database for high-performance prediction of atomic charges. We used the ab initio electronic structure data representing calcium ions and the structures of the disordered segments of calcium-binding peptides with surrounding water molecules to train several explainable models. Network theory was used to extract the topological features of atomic interactions in the structurally complex data dictated by the coordination chemistry of a calcium ion, a potent indicator of its charge state in protein. Our design created a computational tool of Ca^XML, which provided a framework of explainable machine learning model to annotate ionic charges of calcium ions in calcium-binding proteins in response to the chemical changes in an environment. Our framework will provide new insights into protein design for engineering functionality based on the limited size of scientific data in a genome space.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 2","pages":"e70023"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047684","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":"Cryo-EM SPR structures of Salmonella typhimurium ArnC; the key enzyme in lipid-A modification conferring polymyxin resistance.","authors":"Dhruvin H Patel, Elina Karimullina, Yirui Guo, Cameron Semper, Deepak T Patel, Tabitha Emde, Dominika Borek, Alexei Savchenko","doi":"10.1002/pro.70037","DOIUrl":"10.1002/pro.70037","url":null,"abstract":"<p><p>Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective. Here, we report the cryo-EM SPR structures of glycosyltransferase ArnC from Salmonella typhimurium determined in apo and UDP-bound forms at resolutions 2.75 Å and 3.8 Å, respectively. The structure of the ArnC protomer comprises three distinct regions: an N-terminal glycosyltransferase domain, transmembrane region, and the interface helices (IHs). ArnC forms a tetramer with C2 symmetry, where the C-terminal strand inserts into the adjacent protomer. This tetrameric state is further stabilized by two distinct interfaces formed by ArnC that form a network of hydrogen bonds and salt bridges. The binding of UDP induces conformational changes that stabilize the loop between residues H201 to S213, and part of the putative catalytic pocket formed by IH1 and IH2. The surface property analysis revealed a hydrophobic cavity formed by TM1 and TM2 in the apo state, which is disrupted upon UDP binding. The comparison of ArnC structures to their homologs GtrB and DPMS suggests the key residues involved in ArnC catalytic activity.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 2","pages":"e70037"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047686","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":"Engineered protein G variants for multifunctional antibody-based assemblies.","authors":"Tomasz Slezak, Kelly M O'Leary, Jinyang Li, Ahmed Rohaim, Elena K Davydova, Anthony A Kossiakoff","doi":"10.1002/pro.70019","DOIUrl":"10.1002/pro.70019","url":null,"abstract":"<p><p>We have developed a portfolio of antibody-based modules that can be prefabricated as standalone units and snapped together in plug-and-play fashion to create uniquely powerful multifunctional assemblies. The basic building blocks are derived from multiple pairs of native and modified Fab scaffolds and protein G (PG) variants engineered by phage display to introduce high pair-wise specificity. The variety of possible Fab-PG pairings provides a highly orthogonal system that can be exploited to perform challenging cell biology operations in a straightforward manner. The simplest manifestation allows multiplexed antigen detection using PG variants fused to fluorescently labeled SNAP-tags. Moreover, Fabs can be readily attached to a PG-Fc dimer module which acts as the core unit to produce plug-and-play IgG-like assemblies, and the utility can be further expanded to produce bispecific analogs using the \"knobs into holes\" strategy. These core PG-Fc dimer modules can be made and stored in bulk to produce off-the-shelf customized IgG entities in minutes, not days or weeks by just adding a Fab with the desired antigen specificity. In another application, the bispecific modalities form the building block for fabricating potent bispecific T-cell engagers (BiTEs), demonstrating their efficacy in cancer cell-killing assays. Additionally, the system can be adapted to include commercial antibodies as building blocks, greatly increasing the target space. Crystal structure analysis reveals that a few strategically positioned interactions engender the specificity between the Fab-PG variant pairs, requiring minimal changes to match the scaffolds for different possible combinations. This plug-and-play platform offers a user-friendly and versatile approach to enhance the functionality of antibody-based reagents in cell biology research.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 2","pages":"e70019"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047690","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":"Methods for detecting, building, and improving tryptophan mannosylation in glycoprotein structures.","authors":"Lou Holland, Phuong Thao Pham, Haroldas Bagdonas, Jordan S Dialpuri, Lucy C Schofield, Jon Agirre","doi":"10.1002/pro.70025","DOIUrl":"10.1002/pro.70025","url":null,"abstract":"<p><p>Tryptophan mannosylation, the covalent addition of an α-ᴅ-mannose sugar to a tryptophan side chain, is a post-translational modification (PTM) that can affect protein stability, folding, and interactions. Compared to other forms of protein glycosylation, it is relatively uncommon but is affected by conformational anomalies and modeling errors similar to those seen in N- and O-glycans in the Protein Data Bank (PDB). In this work, we report methods for detecting, building, and improving mannose structures linked to tryptophans. These methods have been used to mine X-ray crystallographic and cryo-electron microscopy maps in the PDB looking for unmodeled mannosylation, resulting in a number of cases where the modification can be placed in the map with high confidence. Additionally, we address most conformational issues affecting this modification. Finally, the development of a structural template to recognize thrombospondin repeats (TSR) domains where tryptophan mannosylation occurs will allow for the mannosylation of candidate-predicted models, for example, those predicted with AlphaFold.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 2","pages":"e70025"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010472","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":"Accelerated amyloid fibril formation at the interface of liquid-liquid phase-separated droplets by depletion interactions.","authors":"Keiichi Yamaguchi, Joji Mima, Kichitaro Nakajima, Hiroki Sakuta, Kenichi Yoshikawa, Yuji Goto","doi":"10.1002/pro.5163","DOIUrl":"10.1002/pro.5163","url":null,"abstract":"<p><p>Amyloid fibril formation of α-synuclein (αSN) is a hallmark of synucleinopathies. Although the previous studies have provided numerous insights into the molecular basis of αSN amyloid formation, it remains unclear how αSN self-assembles into amyloid fibrils in vivo. Here, we show that αSN amyloid formation is accelerated in the presence of two macromolecular crowders, polyethylene glycol (PEG) (MW: ~10,000) and dextran (DEX) (MW: ~500,000), with a maximum at approximately 7% (w/v) PEG and 7% (w/v) DEX. Under these conditions, the two crowders induce a two-phase separation of upper PEG and lower DEX phases with a small number of liquid droplets of DEX and PEG in PEG and DEX phases, respectively. Fluorescence microscope images revealed that the interfaces of DEX droplets in the upper PEG phase are the major sites of amyloid formation. We consider that the depletion interactions working in micro phase-segregated state with DEX and PEG systems causes αSN condensation at the interface between solute PEG and DEX droplets, resulting in accelerated amyloid formation. Ultrasonication further accelerated the amyloid formation in both DEX and PEG phases, confirming the droplet-dependent amyloid formation. Similar PEG/DEX-dependent accelerated amyloid formation was observed for amyloid β peptide. In contrast, amyloid formation of β₂-microglobulin or hen egg white lysozyme with a native fold was suppressed in the PEG/DEX mixtures, suggesting that the depletion interactions work adversely depending on whether the protein is unfolded or folded.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 2","pages":"e5163"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060527","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":"Conformational dynamics in specialized C₂H₂ zinc finger domains enable zinc-responsive gene repression in S. pombe.","authors":"Vibhuti Wadhwa, Cameron Jamshidi, Kye Stachowski, Amanda J Bird, Mark P Foster","doi":"10.1002/pro.70044","DOIUrl":"10.1002/pro.70044","url":null,"abstract":"<p><p>Loz1 is a zinc-responsive transcription factor in fission yeast that maintains cellular zinc homeostasis by repressing the expression of genes required for zinc uptake in high zinc conditions. Previous deletion analysis of Loz1 found a region containing two tandem C₂H₂ zinc-fingers and an upstream \"accessory domain\" rich in histidine, lysine, and arginine residues to be sufficient for zinc-dependent DNA binding and gene repression. Here we report unexpected biophysical properties of this pair of seemingly classical C₂H₂ zinc fingers. Isothermal titration calorimetry and NMR spectroscopy reveal two distinct zinc binding events localized to the zinc fingers. NMR spectra reveal complex dynamic behavior in this zinc-responsive region spanning time scales from fast 10^-12-10^-10 to slow >10⁰ s. Slow exchange due to cis-trans isomerization of the TGERP linker results in the doubling of many signals in the protein. Conformational exchange on the 10^-3 s timescale throughout the first zinc finger distinguishes it from the second and is linked to a weaker affinity for zinc. These findings reveal a mechanism of zinc sensing by Loz1 and illuminate how the protein's rough free-energy landscape enables zinc sensing, DNA binding and regulated gene expression.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 2","pages":"e70044"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047685","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}