{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360584340527770240.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1016/j.ijbiomac.2023.127933"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0141813023048328?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0141813023048328?httpAccept=text/plain"}},{"identifier":{"@type":"PMID","@value":"37939764"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Unveiling the structural and functional consequences of the p.D109G pathogenic mutation in human αB-Crystallin responsible for restrictive cardiomyopathy and skeletal myopathy"}],"description":[{"notation":[{"@value":"αB-Crystallin (αB-Cry) is expressed in many tissues, and mutations in this protein are linked to various diseases, including cataracts, Alzheimer's disease, Parkinson's disease, and several types of myopathies and cardiomyopathies. The p.D109G mutation, which substitutes a conserved aspartate residue involved in the interchain salt bridges, with glycine leads to the development of both restrictive cardiomyopathy (RCM) and skeletal myopathy. In this study, we generated this mutation in the α-Cry domain (ACD) which is crucial for forming the active chaperone dimeric state, using site-directed mutagenesis. After inducing expression in the bacterial host, we purified the mutant and wild-type recombinant proteins using anion exchange chromatography. Various spectroscopic evaluations revealed significant changes in the secondary, tertiary, and quaternary structures of human αB-Cry caused by this mutation. Furthermore, this pathogenic mutation led to the formation of protein oligomers with larger sizes than those of the wild-type protein counterpart. The mutant protein also exhibited increased chaperone activity and decreased chemical, thermal, and proteolytic stability. Atomic force microscopy (AFM), transmission electron microscopy (TEM), and fluorescence microscopy (FM) demonstrated that p.D109G mutant protein is more prone to forming amyloid aggregates. The misfolding associated with the p.D109G mutation may result in abnormal interactions of human αB-Cry with its natural partners (e.g., desmin), leading to the formation of protein aggregates. These aggregates can interfere with normal cellular processes and may contribute to muscle cell dysfunction and damage, resulting in the pathogenic involvement of the p.D109G mutant protein in restrictive cardiomyopathy and skeletal myopathy."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380584340527770504","@type":"Researcher","foaf:name":[{"@value":"Mehrnaz Hosseini Jafari"}]},{"@id":"https://cir.nii.ac.jp/crid/1380584340527770375","@type":"Researcher","foaf:name":[{"@value":"Mohammad Bagher Shahsavani"}]},{"@id":"https://cir.nii.ac.jp/crid/1380584340527770414","@type":"Researcher","foaf:name":[{"@value":"Masaru Hoshino"}]},{"@id":"https://cir.nii.ac.jp/crid/1380584340527770407","@type":"Researcher","foaf:name":[{"@value":"Jun Hong"}]},{"@id":"https://cir.nii.ac.jp/crid/1380584340527770241","@type":"Researcher","foaf:name":[{"@value":"Ali Akbar Saboury"}]},{"@id":"https://cir.nii.ac.jp/crid/1380584340527770245","@type":"Researcher","foaf:name":[{"@value":"Ali Akbar Moosavi-Movahedi"}]},{"@id":"https://cir.nii.ac.jp/crid/1380584340527770408","@type":"Researcher","foaf:name":[{"@value":"Reza Yousefi"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"01418130"}],"prism:publicationName":[{"@value":"International Journal of Biological Macromolecules"}],"dc:publisher":[{"@value":"Elsevier BV"}],"prism:publicationDate":"2024-01","prism:volume":"254","prism:startingPage":"127933"},"reviewed":"false","dc:rights":["https://www.elsevier.com/tdm/userlicense/1.0/","https://www.elsevier.com/legal/tdmrep-license","http://www.elsevier.com/open-access/userlicense/1.0/","https://doi.org/10.15223/policy-017","https://doi.org/10.15223/policy-037","https://doi.org/10.15223/policy-012","https://doi.org/10.15223/policy-029","https://doi.org/10.15223/policy-004"],"url":[{"@id":"https://api.elsevier.com/content/article/PII:S0141813023048328?httpAccept=text/xml"},{"@id":"https://api.elsevier.com/content/article/PII:S0141813023048328?httpAccept=text/plain"}],"createdAt":"2023-11-06","modifiedAt":"2025-09-26","project":[{"@id":"https://cir.nii.ac.jp/crid/1040854882537449984","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"22K06101"},{"@type":"JGN","@value":"JP22K06101"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K06101/"}],"notation":[{"@language":"ja","@value":"天然変性領域を介した分子認識機構の解明"},{"@language":"en","@value":"Mechanism of molecular recognition between intrinsically disordered regions."}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050568617196363008","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Elucidation of the mechanism of subunit exchange in αB crystallin oligomers"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011143543934464","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Interaction of the Molecular Chaperone αB-Crystallin with α-Synuclein: Effects on Amyloid Fibril Formation and Chaperone Activity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011144024958848","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Chaperone-Mediated Autophagy"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011144809672448","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Cataract-Causing Defect of a Mutant γ-Crystallin Proceeds through an Aggregation Pathway Which Bypasses Recognition by the α-Crystallin Chaperone"}]},{"@id":"https://cir.nii.ac.jp/crid/1360011145423597056","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"A novel CRYAB mutation resulting in multisystemic disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360013170317882880","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Peak Fitting Applied to Fourier Transform Infrared and Raman Spectroscopic Analysis of Proteins"}]},{"@id":"https://cir.nii.ac.jp/crid/1360021394452299264","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The specificity of the interaction between<i>α</i>B-crystallin and desmin filaments and its impact on filament aggregation and cell viability"}]},{"@id":"https://cir.nii.ac.jp/crid/1360021396133084928","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The congenital cataract‐causing mutations P20R and A171T are associated with important changes in the amyloidogenic feature, structure and chaperone‐like activity of human αB‐crystallin"}]},{"@id":"https://cir.nii.ac.jp/crid/1360292619603050240","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Chaperone activity of alpha-crystallins modulates intermediate filament assembly."}]},{"@id":"https://cir.nii.ac.jp/crid/1360302868757424000","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The impact of Hydrogen peroxide on structure, stability and functional properties of Human R12C mutant αA-crystallin: The imperative insights into pathomechanism of the associated congenital cataract incidence"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302871992754176","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Amyloid formation of bovine insulin is retarded in moderately acidic pH and by addition of short-chain alcohols"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574093832590848","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Macromolecular Size-and-Shape Distributions by Sedimentation Velocity Analytical Ultracentrifugation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574095404842496","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Desmin myopathy: a multisystem disorder involving skeletal, cardiac, and smooth muscle"}]},{"@id":"https://cir.nii.ac.jp/crid/1360584344410489216","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The biochemical association between R157H mutation in human αB-crystallin and development of cardiomyopathy: Structural and functional analyses of the mutant protein"}]},{"@id":"https://cir.nii.ac.jp/crid/1360584345435517952","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Investigating the role of double mutations R12C/P20R, and R12C/R69C on structure, chaperone-like activity, and amyloidogenic properties of human αB-crystallin"}]},{"@id":"https://cir.nii.ac.jp/crid/1360584346103307776","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Effect of Phosphorylation on αB-crystallin: Differences in Stability, Subunit Exchange and Chaperone Activity of Homo and Mixed Oligomers of αB-Crystallin and its Phosphorylation-mimicking Mutant"}]},{"@id":"https://cir.nii.ac.jp/crid/1360584346103424640","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Interaction of human recombinant αA‐ and αB‐crystallins with early and late unfolding intermediates of citrate synthase on its thermal denaturation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360584346104051200","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Macroautophagy and Chaperone‐Mediated Autophagy in Heart Failure: The Known and the Unknown"}]},{"@id":"https://cir.nii.ac.jp/crid/1360584346104095232","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Mechanism of Cataract Formation in αA-crystallin Y118D Mutation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360584346104214912","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Missense Mutations in CRYAB Are Liable for Recessive Congenital Cataracts"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855570891060736","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Size-Distribution Analysis of Macromolecules by Sedimentation Velocity Ultracentrifugation and Lamm Equation Modeling"}]},{"@id":"https://cir.nii.ac.jp/crid/1360855570933375616","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Mouse Model of Desmin-Related Cardiomyopathy"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861710584078464","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Upregulation of alphaB-crystallin expression in the substantia nigra of patients with Parkinson's disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861712138854784","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Neuromuscular Diseases Due to Chaperone Mutations: A Review and Some New Results"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865818726282752","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Modulation of α‐crystallin chaperone activity: A target to prevent or delay cataract?"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865818726549248","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Alpha B-Crystallin Overexpression Protects Oligodendrocyte Precursor Cells Against Oxidative Stress-Induced Apoptosis Through the Akt Pathway"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865818726945792","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Mechanism of Insolubilization by a Single-Point Mutation in αA-Crystallin Linked with Hereditary Human Cataracts"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865818727169152","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Mechanism of Small Heat Shock Protein Function in Vivo"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865818727806336","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"An AFM Approach Applied in a Study of α-Crystallin Membrane Association: New Insights into Lens Hardening and Presbyopia Development"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865819403004288","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Interaction of the chaperones alpha B-crystallin and CHIP with fibrillar alpha-synuclein: Effects on internalization by cells and identification of interacting interfaces"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865819403091712","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Evaluation of structure, chaperone-like activity and protective ability of peroxynitrite modified human α-Crystallin subunits against copper-mediated ascorbic acid oxidation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865819403530752","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Altered Chaperone-like Activity of α-Crystallins Promotes Cataractogenesis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865819403534336","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"HSPB5 engages multiple states of a destabilized client to enhance chaperone activity in a stress-dependent manner"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865819404130944","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Structural and Functional Peculiarities of α-Crystallin"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865820412101376","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The novel αB‐crystallin (\n            <i>CRYAB</i>\n            ) mutation p.D109G causes restrictive cardiomyopathy"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865820412432000","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Abnormal interaction of motor neuropathy-associated mutant HspB8 (Hsp22) forms with the RNA helicase Ddx20 (gemin3)"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865820412465280","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Increased chaperone activity of human α‌B-crystallin with incomplete oxidation as a new defense mechanism against oxidative stress"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865820413384192","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"αB-Crystallin Modulates Protein Aggregation of Abnormal Desmin"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865820413606784","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Crosstalk Between Chaperone-Mediated Protein Disaggregation and Proteolytic Pathways in Aging and Disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865820927872512","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"What to use to express the variability of data: Standard deviation or standard error of mean?"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137043527904000","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Raman spectroscopy of protein pharmaceuticals"}]},{"@id":"https://cir.nii.ac.jp/crid/1361137045089512576","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"How to measure and predict the molar absorption coefficient of a protein"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418519625992448","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Genealogy of the α-crystallin—small heat-shock protein superfamily"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418519710492160","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Molecular insights into cardiomyopathies associated with desmin (DES) mutations"}]},{"@id":"https://cir.nii.ac.jp/crid/1361418521229884032","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"αB-crystallin mutation in dilated cardiomyopathy"}]},{"@id":"https://cir.nii.ac.jp/crid/1361981468827408512","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The Interaction of αB-Crystallin with Mature α-Synuclein Amyloid Fibrils Inhibits Their Elongation"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262943735019520","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"The coming of age of chaperone-mediated autophagy"}]},{"@id":"https://cir.nii.ac.jp/crid/1362262944048486400","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Alpha B-crystallin in cardiac tissue. Association with actin and desmin filaments."}]},{"@id":"https://cir.nii.ac.jp/crid/1362262946057309312","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Interplay of LRRK2 with chaperone-mediated autophagy"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544421121417856","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Alpha-crystallin can function as a molecular chaperone."}]},{"@id":"https://cir.nii.ac.jp/crid/1362544421235812480","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Comparison of scanning electron microscopy, dynamic light scattering and analytical ultracentrifugation for the sizing of poly(butyl cyanoacrylate) nanoparticles"}]},{"@id":"https://cir.nii.ac.jp/crid/1362544421287820544","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Interpretation of the doublet at 850 and 830 cm<sup>-1</sup> in the Raman spectra of tyrosyl residues in proteins and certain model compounds"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825893533298432","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Amyloid Fibril Formation by Lens Crystallin Proteins and Its Implications for Cataract Formation"}]},{"@id":"https://cir.nii.ac.jp/crid/1362825895537392256","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Equilibrium thermal transitions of collagen model peptides"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388843641877376","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Human resistin, a proinflammatory cytokine, shows chaperone-like activity"}]},{"@id":"https://cir.nii.ac.jp/crid/1363388844152481024","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Genetics of crystallins: Cataract and beyond"}]},{"@id":"https://cir.nii.ac.jp/crid/1363670319876254080","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Intermediate filament interactions can be altered by HSP27 and αB-crystallin"}]},{"@id":"https://cir.nii.ac.jp/crid/1363951794840466176","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Lens aging: Effects of crystallins"}]},{"@id":"https://cir.nii.ac.jp/crid/1363951795152696064","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Mutation R120G in αB-crystallin, which is linked to a desmin-related myopathy, results in an irregular structure and defective chaperone-like function"}]},{"@id":"https://cir.nii.ac.jp/crid/1364233269395596416","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"α‐crystallin: a review of its structure and function"}]},{"@id":"https://cir.nii.ac.jp/crid/1364233270307669376","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"A missense mutation in the αB-crystallin chaperone gene causes a desmin-related myopathy"}]},{"@id":"https://cir.nii.ac.jp/crid/1370584340527770253","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Yu, fluorescence and Raman spectroscopy of the crystalline lens"}]},{"@id":"https://cir.nii.ac.jp/crid/1370584340527770256","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Therapeutic potential of α-crystallin"}]},{"@id":"https://cir.nii.ac.jp/crid/1370584340527770261","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Structural and functional properties of NH2-terminal domain, core domain, and COOH-terminal extension of αA-and αB-crystallins"}]},{"@id":"https://cir.nii.ac.jp/crid/1370584340527770384","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Differential role of arginine mutations on the structure and functions of α-crystallin"}]},{"@id":"https://cir.nii.ac.jp/crid/1370584340527770394","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Structure and function of α-crystallins: traversing from in vitro to in vivo"}]},{"@id":"https://cir.nii.ac.jp/crid/1370584340527770395","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Molecular insights into the interaction of 5-fluorouracil and Fe3O4 nanoparticles with beta-casein: an experimental and theoretical study"}]},{"@id":"https://cir.nii.ac.jp/crid/1370584340527770497","@type":"Product","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Developing a novel exenatide-based incretin mimic (αB-ex): expression, purification and structural-functional characterization"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1016/j.ijbiomac.2023.127933"},{"@type":"KAKEN","@value":"PRODUCT-24918627"},{"@type":"OPENAIRE","@value":"doi_dedup___::ab05499d4fca7e9f25cd15a01820af9f"}]}