Biochimica et biophysica acta. Proteins and proteomics最新文献

{"title":"Solution-based studies on the contact between the complement receptor 3 ligand-binding domain and simvastatin","authors":"Morten Hulbæk Fog ,&nbsp;Violaine Hubert ,&nbsp;Corinne Sanglar ,&nbsp;Marie Martin ,&nbsp;Ines Hristovska ,&nbsp;Szilvia Karpati ,&nbsp;Frédéric Lerouge ,&nbsp;Stéphane Parola ,&nbsp;Olivier Pascual ,&nbsp;Marlène Wiart ,&nbsp;Jean-Marc Lancelin ,&nbsp;Thomas Vorup-Jensen ,&nbsp;Florence Guillière","doi":"10.1016/j.bbapap.2025.141096","DOIUrl":"10.1016/j.bbapap.2025.141096","url":null,"abstract":"<div><div>Simvastatin is a primary cholesterol-lowering medication, but it has also been reported to possess anti-inflammatory properties. Notably, the CD18 integrins are targets for simvastatin antagonism of ligand binding, which may affect leukocyte adhesion and diapedesis. Lymphocyte-associated antigen (LFA)-1 is inhibited through an allosteric mechanism by binding the lactone form of simvastatin (simvastatin-lac) to a hydrophobic pocket in the major ligand binding domain, the alpha chain I domain. By contrast, crystallographic evidence showed that complement receptor 3 (CR3) is inhibited by simvastatin in its carboxylate form (simvastatin-carbox) chelated by an Mg²⁺ ion in the α_MI metal ion-dependent adhesion site (MIDAS). We now report that the affinity (<em>K</em>_D) of simvastatin-carbox for the α_MI is ∼650 μM, which is significantly weaker than the 50 %-inhibitory concentration of simvastatin-lac at 50 μM. The simvastatin-carbox was incapable of inhibiting CR3 binding to iC3b, nor did it exert any neuroprotective or anti-inflammatory effects in the middle cerebral artery occlusion animal model of stroke, unlike what has been reported for simvastatin-lac. From available structural data on the CR3 ligand binding domain in complex with C3d, we suggest that simvastatin-lac makes a critical ternary complex with the ligand binding domain and its ligand before engaging, in its carboxylate form, the MIDAS. In this way, both the LFA-1 and CR3 are antagonized by simvastatin-lac but through fundamentally different mechanisms.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 6","pages":"Article 141096"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879930","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":"Self-association of Apolipoprotein A-I studied with multiple-association models: A pyrene multiparametric analysis.","authors":"Wilson A Tárraga, Lisandro J Falomir-Lockhart, Horacio A Garda, Marina C Gonzalez","doi":"10.1016/j.bbapap.2025.141093","DOIUrl":"10.1016/j.bbapap.2025.141093","url":null,"abstract":"<p><p>Apolipoprotein A-I (apoA-I) is the main protein of high-density lipoprotein particles, conferring anti-atherogenic properties through reverse cholesterol transport. In its lipid-free state, apoA-I self-associates, a process implicated in normal physiology as well as in pathological conditions, such as amyloidosis. Although various mechanisms have been proposed to explain its self-association, there is still no consensus, and its functional implications remain unclear. Here, we employed a multi-parametric fluorescent probe to investigate apoA-I self-association. We used three single cysteine mutants located in different helixes: K107C (H4), K133C (H5), and F225C (H10); and labelled them with pyrene as detailed previously (Tárraga et al. Arch Biochem Biophys 699 (2021) 108748). Our original experiments revealed excimer emission between helixes H5 and H10 and polarity changes also in H4. By exploiting specific pyrene band emissions to monitor dimer association (via excimer formation) and microenvironment polarity (P-value), we tracked apoA-I oligomerization as a function of protein concentration. Several mathematical models of self-association were developed and compared using selection criteria to identify the simplest model reproducing apoA-I's complex behaviour in aqueous media: a Sequential Association submodel limited to a tetramer as the highest order oligomeric species and considering both dimers and tetramers as responsible for the excimer's emission. Multi-equilibria models enhanced the titration analysis, allowing estimation of association constants (Ka) and oligomeric species distribution. Our results support previous evidence that contacts among helixes, which stabilize discoidal HDL particles, are already present in lipid-free apoA-I, with dimeric species predominating, and possible tetrameric too. Further investigation of these species is essential to elucidate their physiological and pathological roles, such as in atherosclerosis.</p>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":" ","pages":"141093"},"PeriodicalIF":2.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803338","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":"Obituary - Per Jemth","authors":"Stefano Gianni ,&nbsp;Ylva Ivarsson ,&nbsp;Kristian Strømgaard","doi":"10.1016/j.bbapap.2025.141068","DOIUrl":"10.1016/j.bbapap.2025.141068","url":null,"abstract":"","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 5","pages":"Article 141068"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723897","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":"Unravelling the phosphoregulatory network of protein kinase C-delta (PKC-δ)","authors":"Darshan Hebbal Raghu ,&nbsp;Leona Dcunha ,&nbsp;Mukhtar Ahmed ,&nbsp;Amal Fahma ,&nbsp;Althaf Mahin ,&nbsp;Athira Perunelly Gopalakrishnan ,&nbsp;Levin John ,&nbsp;Suhail Subair ,&nbsp;Prathik Basthikoppa Shivamurthy ,&nbsp;Susmi Varghese ,&nbsp;Samseera Ummar ,&nbsp;Mahammad Nisar ,&nbsp;Poornima Ramesh ,&nbsp;Inamul Hasan Madar ,&nbsp;Rajesh Raju","doi":"10.1016/j.bbapap.2025.141080","DOIUrl":"10.1016/j.bbapap.2025.141080","url":null,"abstract":"<div><div>Protein kinase C Delta (PRKCD) is a serine/threonine kinase involved in transcription regulation, cytoskeleton organization, DNA damage response, DNA repair and carcinogenesis. Several PRKCD phosphopeptides are frequently detected to be differentially regulated through mass spectrometry-based phosphoproteomics analysis. Here, we utilize publicly available phosphoproteomics data to decipher phosphoregulatory networks associated with PRKCD. Among 315 phosphoproteomics datasets demonstrating the differential regulation of phosphopeptides of PRKCD, the phosphosites S304, Y313, S645, S299, S302, S664, Y334, Y374, T295 and T507 predominantly represent PRKCD hyperphosphorylation in over 83 % of cases. Further, through co-differential regulation analysis of the predominant sites and associated phosphosites on other proteins, we propose that the autophosphorylation sites S302 and S304 are critically associated with the kinase activity of PRKCD and play a crucial role in modulating its downstream signaling pathways. Compared to known activation sites of PRKCD including Y313, Y334 and Y374, the sites S302 and S304 coregulated the most with the experimentally validated and predicted substrates. Besides that, phosphosites Y313, Y334 and Y374 are associated with stress signaling and cancer progression. Current study focuses on critical kinase-activation associated with phosphosites in kinases. This study highlights the sites S302 and S304 as activation sites and as key players in various cellular processes including cell cycle regulation, motility, adhesion and migration. Our approach and the stringent criteria adopted sets a robust platform to analyze differentially regulated phosphoproteome data in diverse biological contexts to interpret the predominant phosphosites, their co-regulation and the overall biological relevance of such regulation in pathophysiological processes.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 5","pages":"Article 141080"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212244","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":"Oxygen-carrying proteins employed in blood substitute candidates: differences in interactions with a model antioxidant molecule","authors":"Maria Lehene ,&nbsp;Jozsef Simon ,&nbsp;Cezara Zagrean-Tuza ,&nbsp;Andreea Aghion ,&nbsp;Bianca Vasile ,&nbsp;Alexandru Sonica ,&nbsp;Stefania Iancu ,&nbsp;Radu Silaghi-Dumitrescu","doi":"10.1016/j.bbapap.2025.141086","DOIUrl":"10.1016/j.bbapap.2025.141086","url":null,"abstract":"<div><div>Glutaraldehyde-polymerized hemoglobin (poly-Hb) has long been explored as a key candidate for blood substitute compositions, to be used in transfusions in order to supplement the oxygen-carrying capacity following severe blood loss. Bovine hemoglobin (bHb) has been the standard choice for such efforts, due to its reasonable availability and to its reduced dependence on organic allosteric effectors. We have recently shown that poly-Hb produced from ovine Hb (poly-oHb) outperforms poly-bHb in in vivo tests employing transfusion after up to 30 % blood loss in animals. This improvement was found to correlate with an increased resistance of ovine hemoglobin (oHb) and of poly-oHb towards oxidative and nitrosative stress agents in vitro. The molecular bases for these differences in reactivity offer an interesting challenge, given the high sequence homology between vertebrate hemoglobins. Reported here is an investigation of these molecular bases using different spectroscopic (fluorescence, resonance Raman, NMR, EPR) and computational (molecular docking) methods to assess the interaction with a convenient probe ligand representative of the class of natural antioxidants, caffeic acid. Fluorescence experiments reveal that ovine Hb fluorescence saturates above 25 μM caffeic acid and indicating full occupancy of fluorescence-responsive binding sites, while resonance Raman and NMR data indicate signals for the heme and indicate the differences between the types of Hbs and the antioxidant binding behavior after polymerization. Computational docking corroborated the spectroscopic data by identifying aromatic residues and distinct affinity patterns for caffeate. The results show that structural differences in oHb may explain a higher redox stability.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 5","pages":"Article 141086"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279606","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":"Elucidation of multifunctionality and substrate specificity of human aspartate aminotransferases","authors":"Tetsuya Miyamoto ,&nbsp;Haruna Kito ,&nbsp;Karen Sato ,&nbsp;Toshihiko Sugiki ,&nbsp;Kumiko Sakai-Kato","doi":"10.1016/j.bbapap.2025.141081","DOIUrl":"10.1016/j.bbapap.2025.141081","url":null,"abstract":"<div><div><span>d</span>-Serine and <span>d</span>-aspartate play crucial physiological roles in mammals. <span>d</span>-Serine is produced by serine racemase, but the biosynthetic pathway of <span>d</span>-aspartate remains unclear. In this study, we investigated the substrate specificity and multifunctionality of human aspartate aminotransferases (hGOT1 and hGOT2) to reveal whether they possess <span>d</span>-Amino acid metabolic activity. Neither enzyme displayed racemase activity toward various amino acids including aspartate, although slight alanine racemase activity was detected. Likewise, neither exhibited lyase, dehydratase, or aspartate decarboxylase activities. Regarding aminotransferase activity, both displayed high activity toward <span>l</span>-aspartate and <span>l</span>-glutamate as amino donors, and they acted on some <span>l</span>-Amino acids, but not <span>d</span>-Amino acids. Intriguingly, we found that aminotransferase activity for oxaloacetate followed sigmoidal kinetics rather than typical Michaelis-Menten kinetics. Thermal shift assay experiments suggested that pyridoxal-5′-phosphate and oxaloacetate are involved in protein stability and the ability to bind oxaloacetate is different from hGOT1 and hGOT2. In summary, hGOTs accept some amino donors and acceptors and unique capacity to bind oxaloacetate.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 5","pages":"Article 141081"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198215","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":"Human mitochondrial pyrophosphatase hPPA2: In vitro and in silico study of the factors affecting its function","authors":"Svetlana Kurilova ,&nbsp;Nataliya Vorobyeva ,&nbsp;Ekaterina Bezpalaya ,&nbsp;Marina Serebryakova ,&nbsp;Elena Rodina","doi":"10.1016/j.bbapap.2025.141085","DOIUrl":"10.1016/j.bbapap.2025.141085","url":null,"abstract":"<div><div>Biallelic mutations in a nuclear gene PPA2 in human encoding mitochondrial inorganic pyrophosphatase hPPA2 cause mitochondrial disfunctions leading to severe cardiac pathology. This protein catalyzes a Mg²⁺-dependent hydrolysis of pyrophosphate, a by-product of many biosynthetic reactions, thereby providing a thermodynamic pull for these reactions. In order to better understand molecular mechanisms of mitochondrial disfunction caused by mutations in PPA2 gene, detailed characterization of a metabolic role of hPPA2 is required. In this work, we study the <em>in vitro</em> effects of a panel of metabolites, as well as other factors, on the recombinant hPPA2 activity. This study is complemented with the <em>in silico</em> assessment of possible mechanisms of observed patterns. We demonstrate that at Mg²⁺ concentrations typical for the mitochondrial matrix hPPA2 works at under-saturation and therefore the regulatory factors changing Mg²⁺ concentration will have a significant impact on hPPA2 activity. We also demonstrate that hPPA2 activity is regulated by a redox state of cysteine residues. Mass-spectrometry analysis reveals four Cys residues modified by 4-hydroxy-Hg-benzoate, as well as an S<img>S bridge formation within an hPPA2 monomer. Finally, we found that selected metabolites including intermediates of central metabolism affect hPPA2 activity. <em>In silico</em> analysis of hPPA2 allows a structural insight into the observed properties. Of a special interest is an W-loop, unique for PPA2 proteins from animals and shared with acidocalcisomal soluble pyrophosphatases from kinetoplastids, that may be involved in interaction with small-molecule effectors.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 5","pages":"Article 141085"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279605","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":"Biochemical and kinetic properties of quinone oxidoreductase from Leishmania orientalis, a member of medium-chain dehydrogenase/reductase superfamily","authors":"Panu Pimviriyakul ,&nbsp;Sumita Harungsee ,&nbsp;Theerapat Tangsupatawat ,&nbsp;Yuvarun Kapaothong ,&nbsp;Somchart Maenpuen","doi":"10.1016/j.bbapap.2025.141087","DOIUrl":"10.1016/j.bbapap.2025.141087","url":null,"abstract":"<div><div>Soluble quinone oxidoreductase (QOR) is an attractive target for treating leishmaniasis. In this study, a QOR from <em>Leishmania orientalis</em> PCM2 (<em>Lo</em>QOR) was identified as a member of non<img>Zn²⁺ medium-chain dehydrogenase/reductase (MDR) superfamily. Using steady-state and rapid kinetics approaches, it was found that <em>Lo</em>QOR catalyzes the electron transfer from NADH to menadione <em>via</em> ping-pong kinetics which is unusual for this enzyme. The reaction mechanism was proposed accordingly. The modeled structures created by AlphaFold version 3.0 revealed crucial residues, <em>i.e.,</em> Thr131, Tyr134, and Arg268, which may involve the binding to carboxamide group of the NADH nicotinamide ring. The kinetic analysis of the <em>Lo</em>QOR mutants compared to the wild-type revealed that these residues are not essential for overall catalysis. However, the kinetic mechanism of Tyr134Phe, Tyr134His, and Arg268Gln mutants has shifted to the ternary complex (<em>Lo</em>QOR:NADH:menadione) model, except for Thr131Val and Arg268Lys mutants. It is hypothesized that Tyr134 and Arg268 are likely responsible for determining the mode of the catalytic mechanism. Hence, our findings here provide a fundamental insight into the MDR-type QORs and other related non-metal enzymes in the MDR superfamily.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 5","pages":"Article 141087"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367849","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":"Modulation of thermomechanical-induced albumin aggregation by extracts of Centella asiatica","authors":"Laipubam Gayatri Sharma,&nbsp;Sanjana SenthilKumar,&nbsp;Latha Rangan,&nbsp;Lalit M. Pandey","doi":"10.1016/j.bbapap.2025.141088","DOIUrl":"10.1016/j.bbapap.2025.141088","url":null,"abstract":"<div><div>In this study, <em>Centella asiatica</em> extracts obtained through sequential extraction in ethyl acetate (CEE), methanol (CME), and water (CWE) were explored for the inhibition of thermal and thermomechanical-induced aggregation of albumin. Th-T fluorescence assay, dynamic light scattering (DLS), circular dichroism (CD) spectroscopy, and TEM analysis were used to study the aggregation behavior. Although CWE contained fewer compounds than CEE, it exhibits comparable inhibition characteristics as determined by High-Resolution Liquid Chromatography-Mass Spectrometry (HR-LCMS) and High-Performance Liquid Chromatography (HPLC) analyses. The rate of aggregation is decreased 1.64 to 0.96 h⁻¹ (i.e. two-fold) in the presence of extracts from under thermomechanical conditions. This effect correlates with the antioxidant capacity of the extract and is further supported by CD analysis, which showed no significant alteration in the native structure of BSA upon interaction with CWE, highlighting its aggregation-inhibiting potential. Isothermal titration calorimetry (ITC) identified the extract fraction with the highest binding affinity to BSA. Molecular docking studies revealed that chlorogenic acid, one of the most abundant compounds in CWE, interacts with albumin with the highest binding free energy (−9.0 kcal/mol), binding predominantly at Sudlow's sites I and III through hydrophobic interactions and hydrogen bonding. This study underscores the potential of natural compounds in preventing protein aggregation and provides a foundation for further investigation of lead bioactive components.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 5","pages":"Article 141088"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551835","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":"Native structure of the monoclonal therapeutic CD20 antibody ocrelizumab","authors":"Victor G. Chrone ,&nbsp;Johan C. Jespersen ,&nbsp;Daut C. Asani ,&nbsp;Nicole H. Trier ,&nbsp;Soumik Ray ,&nbsp;Francis Berthias ,&nbsp;Martin Willemoës ,&nbsp;Anja Holm ,&nbsp;Jette L. Frederiksen ,&nbsp;Gunnar Houen ,&nbsp;Peter Højrup","doi":"10.1016/j.bbapap.2025.141084","DOIUrl":"10.1016/j.bbapap.2025.141084","url":null,"abstract":"<div><div>Immunoglobulin G (IgG) is fundamental to adaptive immunity and numerous monoclonal IgGs (monoclonal antibodies (MAbs)) have been developed as therapeutics for various diseases, including ocrelizumab (OMAb), a CD20 MAb used for treating multiple sclerosis, and infliximab (IMAb), a tumor necrosis factor MAb used for treating rheumatoid arthritis and other conditions. Understanding structure-function relationships are essential for understanding the mechanisms of action of IgG MAbs and previous results have shown that IgG has a “closed”, “m”-shaped conformation in native form, which may switch to an “open”, “Y”-shaped conformation upon antigen binding or physico-chemical stress. Supported by immunochemical and biophysical methods and by chemical crosslinking mass spectrometry (XL-MS) we show that both OMAb and IMAb conform to this paradigm. By XL-MS, we identified eighty-five high-confidence cross-links that support the native closed state of OMAb, refining our understanding of IgG architecture. Molecular modeling based on these data further corroborates a compact IgG structure, shielding the Fc domain. This structural insight may increase our understanding of immunoglobulin biology and enhance therapeutic MAb design by optimizing stability and efficacy.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 5","pages":"Article 141084"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279607","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}