PROTEIN SCIENCE蛋白质科学
PROTEIN SCIENCE(英文缩写 PROTEIN SCI),ISSN 0961-8368,eISSN 1469-896X,中文译名:蛋白质科学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 6.993 | Q1 |
| 2022 | 8.000 | Q1 |
| 2023 | 4.500 | Q1 |
| 2024 | 5.200 | Q1 |
| 2025 | 5.600 | Q1 |
PROTEIN SCIENCE 最新收录文献
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1. Quantum Biology 2.0: Traversing and harnessing protein superhighway networks of light and life.
PMID:日期:2026-10-01As an emergent field stimulated by insights from the biological, chemical, physical, and quantum sciences, quantum biology explores how quantum phenomena such as superradiance, tunneling, and entanglement can be leveraged to enhance, influence, and probe biological processes across a diversity of scales and physical degrees of freedom. This review surveys key theoretical, computational, and experimental developments over the last decade, providing relevant historical background and scientific context going back as far as Bohr's 1932 lecture on "Light and Life" in Copenhagen. Reflecting major new areas of investigation, biophysical intuitions, and advancements in critical areas of study from earlier decades, we highlight superradiance and quantum cooperativity; exciton-phonon interactions and long-range electrodynamic organization; quantum tunneling, entanglement, and dispersion effects in protein processes; ultraweak metabolic photon emissions; photosynthesis; magnetosensing and chirality-induced spin dynamics; and emerging quantum technologies employed to delicately observe biosystems or to harness life's complexity and hierarchical order. In each section of the review, we provide foundational information or primers to augment understanding of the underlying physical processes. We highlight various theoretical and experimental milestones while looking forward to new discoveries on these "supremely interesting [and] unsurveyably intricate" protein architectures, which Schrödinger envisioned in What is Life? would serve a far-reaching and consummate purpose of communication and information processing.
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2. {"_":"The lower γ region supports forward rotation in the latter half of the 80° substep of F-ATPase.","sub":["1"]}
PMID:日期:2026-10-01F-ATPase achieves unidirectional rotation of its γ shaft through coordinated conformational cycling of the αβ ring, yet how shaft-ring interactions contribute to the directionality of rotation remains unclear. Here we analyzed an axle-less TF, in which the lower γ region is truncated, by combining single-molecule rotation assays with cryo-EM structural analysis under catalysis conditions. Under ATP-saturated conditions, wild-type TF exhibited three pauses per turn corresponding to the catalytic dwells, whereas axle-less TF exhibited six, revealing an additional intermediate dwell that may be stabilized by γ truncation. This dwell occurred at 40° between the binding and catalytic dwells. High-speed recordings revealed frequent backsteps during the 40° transition between the intermediate and catalytic dwells. Dwell-time analysis indicated an approximately zero free-energy bias between these states, consistent with the absence of a detectable directional bias. Cryo-EM resolved the corresponding binding, intermediate, and catalytic dwell structures, showing a major β conformational change from 0° to 40°, but minimal β rearrangement between 40° and 80°, suggesting that the rotation is not coupled with a large β conformational transition. Thus, the 0-80° step in axle-less TF consists of two regimes: a directional 0-40° motion accompanied by a major β conformational change, followed by a 40-80° interval with little detectable β rearrangement and markedly reduced directional bias. These findings suggest that, in axle-less TF, the latter half of the 80° substep proceeds through thermal diffusion without directional bias, and that the lower γ region may normally help bias this interval toward forward rotation.
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3. Conformational stability and domain-specific structural features of tumor autoantigens regulate autoantibody epitope propensity.
PMID:日期:2026-10-01Autoantibodies against tumor-associated autoantigens are clinically valuable biomarkers for cancer diagnosis; however, the structural determinants governing epitope selectivity remain unknown. Here, we investigated whether the intrinsic conformational stability of target autoantigens regulates the epitope propensity of tumor-associated autoantibodies in non-small cell lung cancer. Using a dual-antigen Luminex bead-based assay that presents each autoantigen in both native and S-cationized denatured forms, we directly compared IgG autoantibody reactivity toward conformational and linear epitopes across 11 autoantigens. Intrinsically disordered aggregation-prone autoantigens, including cancer/testis antigens, NY-ESO-1, and XAGE-1b, predominantly elicit linear epitope-directed responses, whereas thermodynamically stable soluble autoantigens generally drive conformational epitope recognition. Intriguingly, for autoantigens harboring both ordered and disordered segments, the immune response is strictly guided by domain-specific biophysics: while p53-specific antibodies preferentially target their flanking disordered regions, the Wilms' tumor protein 1 exceptionally drives conformational recognition directed toward its structured zinc-finger domains. Recombinant solubility in Escherichia coli broadly correlated with epitope class across all 11 autoantigens, confirming that prokaryotic folding efficiency generally reflects intrinsic conformational stability in vivo for autonomously folding monomeric cytosolic proteins. Independent computational validation was provided by the concordance between the experimental solubility ratios and AlphaFold3-derived Rosetta energy unit/solvent-accessible surface area values, demonstrating the convergence of thermodynamic estimates and patient-derived immune data within a unifying biophysical framework. These findings establish that the autoantibody epitope propensity is closely associated with the thermodynamic stability of the target autoantigen and provide a rational basis for tailoring antigen preparation strategies for autoantibody-based cancer diagnosis.
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4. Engineering a protein homodimer from a heterodimer: A chimeric DBHS protein.
PMID:日期:2026-10-01Drosophila behavior/human splicing (DBHS) proteins are involved at nearly every stage of the RNA lifecycle. There are three paralogues in mammals-SFPQ, NONO and PSPC1-which form both homodimer and heterodimers. It is likely that the non-redundant and overlapping roles of the different DBHS paralogues emerge from their dynamic and combinatorial nature; that is, their ability to mix and match dimer partners. A strong preference for heterodimerisation over homodimerisation has been demonstrated. However, the underlying molecular determinants of DBHS partner preference are poorly understood. This study describes the design, and biochemical and structural characterization of a chimeric DBHS protein designed to be a homodimer with an interface that emulates a DBHS heterodimer. In vitro experiments show that this chimera indeed remains as a homodimer even when in the presence of a native DBHS protein that prefers heterodimerisation. The ease of purification, production of high-quality crystals for X-ray diffraction, and perfect crystallographic symmetry of this engineered homodimer presents this as an attractive approach for future structural studies on DBHS proteins. This ability to engineer partner preference also highlights the potential for DBHS proteins to serve as versatile building blocks in synthetic biology. Furthermore, comparison of the dimer interface of this engineered homodimer with native DBHS proteins highlights subtle conformational differences in residues at the core of the dimer interface, indicating that maximized packing of a core tryptophan residue combined with increased hydrophobic or polar complementarity at the interface is likely to determine DBHS partner preference.
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5. RheoScale 2.0: Revealing the hidden roles of protein positions via substitution patterns.
PMID:日期:2026-10-01A central challenge in molecular biology is understanding how amino acid substitutions modulate various features of protein function and stability. To illuminate the complexities of this relationship, high-throughput (HTP) assays are increasingly used to assess site-saturating mutagenesis libraries. A common downstream analysis is to average the set of 20 outcomes at each amino acid position for comparison with structural and evolutionary features. Average values clearly identify positions that tolerate most substitutions (neutral positions) and positions where most substitutions abolish activity (toggle positions). However, average values conceal the existence of rheostat positions, where different amino acid substitutions sample a wide range of outcomes. To quantitatively identify rheostat positions, we previously developed a histogram-based analysis that we here expand by: (i) incorporating new position classes observed in experimental studies of rheostat positions; (ii) formalizing a hierarchy of class assignments; (iii) refining error-based identification of neutral positions; and (iv) statistically assessing the robustness of class assignments to changes in experimental and computational parameters. RheoScale 2.0 is implemented in Excel and newly implemented in Python for facile integration with existing HTP pipelines; all parameters are customizable. Example analyses are shown for three HTP datasets of the SARS-CoV-2 papain-like protease. Results illustrate two aspects that influence interpretation of HTP data: First, position assignments (and substitution outcomes) depend highly on the measured feature. Second, many protein positions play multiple roles in the sequence-structure-function relationship. The recognition of varied position roles will advance understanding of pathogen evolution, protein engineering, and variant interpretation for personalized medicine.
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6. Integrating the MARTINI2 coarse-grained force field into HADDOCK3 for faster modeling of large biomolecular complexes.
PMID:日期:2026-10-01The integration of coarse-grained (CG) approaches into docking workflows offers a powerful strategy for modeling large biomolecular assemblies with reduced computational costs. We present here the implementation of the MARTINI2 CG force field into the HADDOCK3 integrative modeling platform. This development enables the use of the CG representations and parameters within HADDOCK3 for efficient sampling and scoring of large macromolecular complexes, including protein-protein and protein-nucleic acid complexes. The implementation takes advantage of the modular and flexible architecture of HADDOCK3, allowing a seamless combination of MARTINI2 representation with the various modules. Conversion from and to all-atom models is integrated into the CG modeling workflow. The performance of the protocol is first assessed on protein-protein and protein-DNA benchmarks and then illustrated on a few representative large-scale systems, demonstrating a significant reduction in computational costs while maintaining biologically relevant accuracy. HADDOCK3 is freely available from https://github.com/haddocking/haddock3.
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7. Are hyaluronic acid synthases widely encoded in fungi?
PMID:日期:2026-10-01Hyaluronic acid (HA) is a biologically versatile polysaccharide synthesized by vertebrates and several microbial pathogens. To date, Cryptococcus neoformans CPS1p is the only reported bona fide hyaluronic acid synthase (HAS) in fungi, which is functionally related to bacterial HASs. Considering the phylogenetic and biochemical connection between HASs and chitin synthases (CHSs), essential for fungal cell wall synthesis, it is reasonable to hypothesize the former might be more common in fungi than expected. In this work, a comprehensive in silico survey of putative HASs in the Fungal Tree of Life was carried out. 68 putative HASs, mainly in Basidiomycota, were found, although other artificial intelligence-inferred putative HASs were found among Ascomycota. Global fold and arrangement of essential amino acids were shared by all kingdoms' HASs; however, C. neoformas CPS1p and additional putative fungal HASs (fungal HASs) showed exclusive conserved sequence signatures. Moreover, fungal HASs bore an only 3-helices transmembrane pore and their gating loop, which regulates the entrance of substrates to the catalytic site, was directly connected to an also exclusive intrinsically disordered C-terminus. Phylogenetically, fungal HASs were found in a clade different to that of bacterial, animal and viral HASs, and might share a common ancestor with Class I, III or VI CHSs. The atypical features of fungal HASs could influence the size and biological role of the HA they potentially synthesize and also highlight regulatory differences among HASs at the level of the gating loop configuration.
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8. Strategy for modular assembly of tetravalent, multispecific antibodies.
PMID:日期:2026-10-01Multispecific, multivalent antibodies (Abs) are a burgeoning class of drugs that dramatically expand the pharmacological repertoire beyond traditional therapeutic Abs. Here, we present a simple, modular approach to developing multispecific, multivalent Abs based on a Fab-phage library with a single light chain. Using this library, we created three Abs targeting unique sites on programmed death-ligand 1 (PD-L1) and another antibody targeting CD30. Biophysical and cellular characterization of these Abs demonstrated their functional equivalence to clinically relevant Abs targeting PD-L1 or CD30. We then combined these paratopes into a series of bispecific, tetravalent, triparatopic Abs that retained the functionality of the parental Abs. Structural analysis of each of the Abs in complex with their cognate antigens demonstrated the adaptability of the common light chain to form diverse paratopes with an array of distinct heavy chains.
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9. The assembly of tetrameric human L-lactate dehydrogenase is regulated by ionic strength, β-NADH binding, cyclic peptides, and long-chain dicarboxylates.
PMID:日期:2026-10-01Lactate dehydrogenases catalyze the reduction of pyruvate to lactate, the generation of which is of importance for the energetic metabolism of malignant cells. In particular, human cancer cells overexpress lactate dehydrogenase A (hLDH-A), whose catalytic activity depends on its assembly into the corresponding homotetramer (denoted as hLDH-5), suggesting that compounds interfering with the protein-protein interactions responsible for the generation of hLDH-5 should represent inhibitors of high selectivity. Not surprisingly, quite a number of competitive inhibitors were designed, synthesized, and tested against hLDH-5. However, only a few representatives of the repertoire accordingly obtained feature an appropriate selectivity. Here we show how the ionic strength and β-NADH binding affect the monomers-to-tetramer hLDH-A transition. Moreover, by taking advantage of the isolation of monomeric hLDH-A at neutral pH, we tested the effectiveness of cyclic peptides and long-chain dicarboxylates in hampering the assembly of hLDH-5. Interestingly, the cyclic peptide LCO15 and the long-chain dicarboxylate crocetin were found to be very effective inhibitors of hLDH-A: the catalytic activity of the enzyme was inhibited by 97% and 86% when these compounds were administered at 40 and 20 μM, respectively. Furthermore, the amount of lactate produced by MCF7 human cancer cells was found to decrease by 30% in the presence of 80 μM crocin (a diester of crocetin). Overall, our observations indicate that the assembly of hLDH-A into catalytically competent hLDH-5 can be appropriately inhibited by means of cyclic peptides and long-chain dicarboxylates.
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10. Conserved Asp233-Asp246 hydrogen bond modulates active site dynamics in class A β-lactamases.
PMID:日期:2026-10-01Rigid enzymes catalyze chemical reactions by stabilizing the transition state through a specific conformation. Catalytic residues are precisely positioned, and enzyme dynamics are kept to a minimum. It is thought that conserved residues around the active site (second-shell residues) play a crucial role in positioning catalytic residues. Asp233 and Asp246 are two highly conserved second-shell residues in class A β-lactamases, rigid enzymes that inactivate β-lactam antibiotics. The two aspartates share a short hydrogen bond, linking β-strands 3 and 4. The role of this interaction in Mycobacterium tuberculosis β-lactamase BlaC was studied by mutating the Asp residues to Ala. Disruption of the hydrogen bond subtly affects the activity and stability of the enzyme, suggesting the interaction helps to fine-tune the active site. The effects are larger for BlaC D246A than for D233A, indicating that effects cannot solely be attributed to the loss of the hydrogen bond. Molecular dynamics calculations indicate a shift in the conformational landscape due to the mutations, altering the conformational equilibria of the catalytic residues toward less active states. The results illustrate that second-shell residues act as a complex network that supports the efficient positioning of the catalytic residues.