Biochimica et biophysica acta. Proteins and proteomics最新文献

{"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":"Structure prediction and engineering of de novo proteins","authors":"Lin Qi ,&nbsp;Mark Isalan","doi":"10.1016/j.bbapap.2025.141100","DOIUrl":"10.1016/j.bbapap.2025.141100","url":null,"abstract":"<div><div><em>De novo</em> proteins represent a challenging frontier at the intersection of evolutionary biology and synthetic biology. Broadly, the term encompasses two distinct categories: naturally evolved <em>de novo</em> proteins, which arise from previously non-coding DNA, and synthetically designed <em>de novo</em> proteins, which are created from scratch through computational and experimental methods. This review provides an overview of the definitions, history, functional significance, and investigation methods for both categories. By examining potential challenges in current <em>de novo</em> protein research, this review highlights the growing convergence between natural evolutionary processes and rational protein engineering, reflecting their importance in biological discovery and human innovations.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1874 1","pages":"Article 141100"},"PeriodicalIF":2.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079608","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":"Understanding Huntingtin protein aggregation in cell mimicking environments","authors":"Apurva Mishra,&nbsp;Pramit K. Chowdhury","doi":"10.1016/j.bbapap.2025.141099","DOIUrl":"10.1016/j.bbapap.2025.141099","url":null,"abstract":"<div><div>Protein aggregation plays a crucial role in various neurodegenerative diseases, including Huntington's disease. Understanding the factors influencing aggregation kinetics is essential for deciphering disease mechanisms. This research paper investigates the aggregation of a mutant Huntingtin protein (HD39Q) under various conditions, focusing on the impact of macromolecular crowding agents. The study employs multiple techniques, including fluorescence spectroscopy, circular dichroism, and nanoparticle tracking analysis, to characterize the aggregation kinetics and morphology. The results demonstrate that crowding agents significantly accelerate aggregation, with different agents exhibiting varying effects depending on their physicochemical properties. Fluorescence correlation spectroscopy provides insights into early-stage oligomerization. Confocal and scanning electron microscopy help visualize the resulting aggregates and fibrils. These findings contribute to a better understanding of how intracellular-like environments influence protein aggregation and provide valuable insights into the biophysical properties of aggregation-prone proteins.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1874 1","pages":"Article 141099"},"PeriodicalIF":2.3,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079630","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":"Characterization of fatty acid biosynthesis in microalga Scenedesmus - from the perspective of biofuel production","authors":"Harshit Kumar Sharma ,&nbsp;Ma. Belén Velázquez ,&nbsp;Noelia Marchetti ,&nbsp;Ma. Victoria Busi ,&nbsp;Ajay Kumar ,&nbsp;Julieta Barchiesi ,&nbsp;Chitralekha Nag Dasgupta","doi":"10.1016/j.bbapap.2025.141097","DOIUrl":"10.1016/j.bbapap.2025.141097","url":null,"abstract":"<div><div><em>Scenedesmus quadricauda</em>, a freshwater microalga, has gained attention for its high lipid accumulation potential. However, information on fatty acid (FA) biosynthesis pathways in <em>Scenedesmus</em> species remains limited. Biomass (1.010 gL⁻¹) and lipid content (404 mgL⁻¹) in <em>S. quadricauda</em> were found to be higher compared to other microalgal isolates under autotrophic nutrition. All biodiesel indices were found within the defined range of biodiesel (EN14214) and petro-diesel (EN590:2013) standards. The predominant fatty acid was palmitic acid (16:0), accounting for 33.201 % of the total. Further, homology study and 3D models of all subunits of <em>S. quadricauda</em> enzymes acetyl-CoA carboxylase (ACC) – the key enzyme of the FA biosynthetic pathway - identified distinct structural features. The biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), β-carboxyltransferases (β-CT) subunits of the heteromeric ACC of <em>S. quadricauda</em> showed homology with its eukaryotic counterparts, whereas the α -carboxyltransferases (α-CT) subunit showed homology with prokaryotic carboxyltransferase. In contrast, homologous enzymes in other <em>Scenedesmus</em> species were found to resemble prokaryotic forms exclusively. Conserved motifs such as the glycine-rich loop, ERYV motif, and AAAP motif were identified in the BC and BCCP enzymes. Malonyl-CoA:ACP transacylase (MAT) enzyme of <em>S. quadricauda</em> was of prokaryotic origin but showed structural divergence from its homologs in other <em>Scenedesmus</em> species. Fatty-acyl thioesterases (FAT) enzyme contained a duplication of two 4-hydroxybenzoyl-CoA thioesterase-like domains (4HBT). These unique sequences and binding sites in the fatty acid biosynthesis enzymes of <em>S. quadricauda</em> may contribute to the distinct regulation of carbon flux and lipid assembly compared to other species.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1874 1","pages":"Article 141097"},"PeriodicalIF":2.3,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013758","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":"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":"2025-08-18","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":"Evolution in neuropsychiatric cis-regulatory enhancers through human-specific neuronal mutations within transcription factor binding sites","authors":"Rabail Zehra Raza ,&nbsp;Saad Raza ,&nbsp;Sumayyah Naveed ,&nbsp;Shahid Ali","doi":"10.1016/j.bbapap.2025.141095","DOIUrl":"10.1016/j.bbapap.2025.141095","url":null,"abstract":"<div><div><em>cis</em>-Regulatory elements (CREs) in multicellular genomes play a significant role in precise regulation of the genes. Increasing evidence has shown that alterations in CREs have had a drastic effect on the human brain evolution, neuronal cell adaptation and physiology. The human-specific sequence acceleration in CREs has not only changed the overall cognitive function of the human brain, but also seems to have strongly increased the risk of developing psychiatric disorders. Mapping the human-specific neuronal mutations within CREs remains to be a challenge and can largely impact the way DNA binding domain of the transcription factors interact with the CREs. In this study, we have identified human-specific neuronal mutations within transcription factor binding sites in neuropsychiatric enhancers of three major psychiatric disorders i.e. autism spectrum disorder, schizophrenia and bipolar disorder and studied the impact of human-specific neuronal mutations on binding affinities with the respective transcription factors via molecular dynamic simulation. Moreover, we have also identified signals of positive selection in the same set of empirically confirmed neuropsychiatric enhancers and correlated it with the way transcription factors bind with the human-specific and their counterpart ancestral allele harboring transcription factor binding sites.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 6","pages":"Article 141095"},"PeriodicalIF":2.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858778","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":"The role of the N-terminal p.R56Q mutation in modulating oligomerization and chaperone activity of human αB-crystallin in relation to cardiomyopathy","authors":"Leila Rezaei Somee ,&nbsp;Mansi Upadhyay ,&nbsp;Rahul Shobhawat ,&nbsp;Ashutosh Kumar ,&nbsp;Mohammad Bagher Shahsavani ,&nbsp;Stephanie Simon ,&nbsp;Atiyeh Ghasemi ,&nbsp;Issa Zarei ,&nbsp;Massoud Amanlou ,&nbsp;Ali Akbar Saboury ,&nbsp;Ali Akbar Moosavi-Movahedi ,&nbsp;Reza Yousefi","doi":"10.1016/j.bbapap.2025.141094","DOIUrl":"10.1016/j.bbapap.2025.141094","url":null,"abstract":"<div><div>αB-crystallin (αB-Cry), a critical small heat shock protein, is crucial for cellular proteostasis, especially in the heart and lens. αB-Cry mutations can disrupt its chaperone activity, leading to pathological conditions such as myopathy, cardiomyopathy, and cataracts. The p.R56Q mutation in the N-terminal domain, a region that participates in oligomerization as well as interactions with key proteins such as desmin and αA-Cry, has been associated with cardiomyopathy. However, its specific pathogenic mechanism is not well understood. This study aimed to elucidate the structural and functional consequences of the p.R56Q mutation. Recombinant p.R56Q αB-Cry was purified by chromatographic methods. Moreover, spectroscopic, microscopic, and computational techniques were employed to assess the influence of the mutation on protein function, structure, and stability. Our findings indicated that the p.R56Q mutation leads to significant alterations in human αB-Cry secondary to quaternary structures. The mutant protein was less stable and more prone to forming amyloid-like aggregates. The p.R56Q αB-Cry also formed larger oligomers and exhibited enhanced chaperone activity compared to its wild-type (Wt) protein counterpart. Interestingly, it had a greater affinity for binding to desmin and αA-Cry. While increased chaperone function might be expected to have protective effects, it could interfere paradoxically with critical cellular processes, such as apoptosis, and thus enhance disease pathogenesis. This research provides new insights into the molecular mechanisms underlying αB-Cry-associated cardiomyopathy by highlighting how the p.R56Q mutation alters structural dynamics and chaperone activity.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 6","pages":"Article 141094"},"PeriodicalIF":2.3,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858779","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":"Corrigendum to ‘Glycoproteomic characterization of Neuropilin-1 reveals critical glycosylation sites for SARS-CoV-2 entry’ [Biochimica et Biophysica Acta (BBA) - proteins and proteomics 1873 (5) (2025) 141089]","authors":"Tuhin Das ,&nbsp;Shuhong Luo ,&nbsp;Panning Wang ,&nbsp;Jianmin Fang ,&nbsp;Asif Shajahan ,&nbsp;Lauren Pepi ,&nbsp;Sabyasachi Dash ,&nbsp;Kino Maravillas ,&nbsp;Rochelle N. Wickramasekara ,&nbsp;Parastoo Azadi ,&nbsp;Ruo-Pan Huang","doi":"10.1016/j.bbapap.2025.141092","DOIUrl":"10.1016/j.bbapap.2025.141092","url":null,"abstract":"","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 6","pages":"Article 141092"},"PeriodicalIF":2.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844295","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":"Structural insights of the complex formed by KRAS G12V and a novel TIG3 peptide","authors":"Min Seon Ha ,&nbsp;Chang Woo Han ,&nbsp;Mi Suk Jeong ,&nbsp;Se Bok Jang","doi":"10.1016/j.bbapap.2025.141091","DOIUrl":"10.1016/j.bbapap.2025.141091","url":null,"abstract":"<div><div>Pancreatic cancer remains a severe malignancy with a dismal 5-year survival rate, and most pancreatic cancer patients harbor KRAS mutations, which are critical targets for anti-cancer drug development. However, the structural characteristics of KRAS present challenges for therapeutic targeting. In this study, we developed a novel peptide derived from TIG3 protein, a type II tumor suppressor, and confirmed its moderate affinity binding to KRAS G12V. X-ray crystallography revealed that this peptide binds near the Switch II domain of KRAS G12V, causing conformational changes likely to affect its activity. Furthermore, the peptide reduced the viability of cancer cell lines harboring the KRAS G12V mutation, thus demonstrating its potential as a KRAS G12V inhibitor. Our results indicate that the developed novel TIG3 peptide is a promising candidate for KRAS-targeted therapy and provide structural insights useful for the development of pancreatic ductal adenocarcinoma therapeutics.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 6","pages":"Article 141091"},"PeriodicalIF":2.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768260","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":"Role of N-terminal of metacaspase of Candida albicans in calcium binding.","authors":"Taiz dos Reis Santos ,&nbsp;Mariana Nascimento Romero Trujilho ,&nbsp;João Pedro Martins Silva Costa ,&nbsp;Laurade Azevedo Maffeis Dalzoto ,&nbsp;Ane Caroline Moreira Duarte ,&nbsp;Karolaine Stella Siqueirade Moraes Valdivia ,&nbsp;Ana Júliade Oliveira Machado ,&nbsp;Vitória Caroline Domingues Rios ,&nbsp;Tatiane Faustino de Moraes ,&nbsp;Wagner Alves de Souza Judice ,&nbsp;Marcelo Ferreira Marcondes ,&nbsp;Maurício Ferreira Marcondes Machado","doi":"10.1016/j.bbapap.2025.141090","DOIUrl":"10.1016/j.bbapap.2025.141090","url":null,"abstract":"<div><div>Metacaspases are members of the CD clan and share structural similarities with mammalian caspases but possess unique features. This study delves into the <em>Candida albicans</em> metacaspase CaMCA-Ia, a type I metacaspase. CaMCA-Ia demonstrates Ca²⁺-dependent autoprocessing and presents a hydrophobic N-terminal, which differs from that of type II metacaspases. Truncated CaMCA-Ia (CaMCA-Ia-ΔN86), lacking 86 N-terminal amino acids, undergoes gradual self-processing and intermolecular processing. Calcium addition induces multistep processing, leading to maturation. Like mammalian caspases, CaMCA-Ia-ΔN86 can activate other molecules, indicate intermolecular activation and accelerating maturation. Distinct binding sites for the full-length and truncated forms of CaMCA-Ia in interaction with Ca²⁺ underscore the N-terminal's role in altering calcium affinity. These findings enhance the understanding of metacaspases' intricate activation and maturation dynamics, offering insights into potential drug targets for pathogenic fungi. The CaMCA mutants D252A, D268A, D299A, and D268/269 A display varied responses to calcium, while the corresponding CaMCA-Ia-ΔN86 mutants exhibit different processing patterns. The D268/299 A mutant showed processing after 48 h of incubation with calcium. Alterations in CaMCA structure and function, such as the deletion of the N-terminus and changes in the aspartates at the calcium-binding site, provide important insights into how CaMCA enzymatic activity and autoprocessing are regulated.</div></div>","PeriodicalId":8760,"journal":{"name":"Biochimica et biophysica acta. Proteins and proteomics","volume":"1873 6","pages":"Article 141090"},"PeriodicalIF":2.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738199","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}