Hannah F. Bradford, Christophe J. Lalaurie, Jayesh Gor, Xin Gao, Charis Pericleous, Stephen J. Perkins, Hannah Britt, Konstantinos Thalassinos, Ian Giles, Anisur Rahman, Mihaela Delcea, Paul A. Dalby, Thomas C.R. McDonnell
{"title":"Plasmin Cleavage of Beta-2-Glycoprotein I Alters its Structure and Ability to Bind to Pathogenic Antibodies","authors":"Hannah F. Bradford, Christophe J. Lalaurie, Jayesh Gor, Xin Gao, Charis Pericleous, Stephen J. Perkins, Hannah Britt, Konstantinos Thalassinos, Ian Giles, Anisur Rahman, Mihaela Delcea, Paul A. Dalby, Thomas C.R. McDonnell","doi":"10.1101/2024.04.12.24305747","DOIUrl":null,"url":null,"abstract":"Beta-2-Glycoprotein I (β2GPI) is the main autoantigenic target of antiphospholipid syndrome (APS) with antibodies leading to clinical manifestations. There are two known structural isomers of β2GPI, a J shape and a circular shaped one. The transition between these structures is incompletely understood, with the functional implications unknown. β2GPI is a substrate of the protease plasmin, which cleaves within the fifth domain of β2GPI leading to altered cellular binding. Very little is currently known regarding the structure and function of this protein variant. We present the first comprehensive structural characterisation plasmin-clipped β2GPI and the associated implications for pathogenic antibody binding to this protein.","PeriodicalId":501212,"journal":{"name":"medRxiv - Rheumatology","volume":"38 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"medRxiv - Rheumatology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.04.12.24305747","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Beta-2-Glycoprotein I (β2GPI) is the main autoantigenic target of antiphospholipid syndrome (APS) with antibodies leading to clinical manifestations. There are two known structural isomers of β2GPI, a J shape and a circular shaped one. The transition between these structures is incompletely understood, with the functional implications unknown. β2GPI is a substrate of the protease plasmin, which cleaves within the fifth domain of β2GPI leading to altered cellular binding. Very little is currently known regarding the structure and function of this protein variant. We present the first comprehensive structural characterisation plasmin-clipped β2GPI and the associated implications for pathogenic antibody binding to this protein.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
