Adhesion mechanism of human beta 2-glycoprotein I to phospholipids based on its crystal structure

B Bouma, P G de Groot, J M H van den Elsen, R B G Ravelli, A Schouten, M J A Simmelink, R H W M Derksen, J Kroon, P Gros

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287 Citations (Scopus)

Abstract

Human beta2-glycoprotein I is a heavily glycosylated five-domain plasma membrane-adhesion protein, which has been implicated in blood coagulation and clearance of apoptotic bodies from the circulation. It is also the key antigen in the autoimmune disease anti-phospholipid syndrome. The crystal structure of beta2-glycoprotein I isolated from human plasma reveals an elongated fish-hook-like arrangement of the globular short consensus repeat domains. Half of the C-terminal fifth domain deviates strongly from the standard fold, as observed in domains one to four. This aberrant half forms a specific phospholipid-binding site. A large patch of 14 positively charged residues provides electrostatic interactions with anionic phospholipid headgroups and an exposed membrane-insertion loop yields specificity for lipid layers. The observed spatial arrangement of the five domains suggests a functional partitioning of protein adhesion and membrane adhesion over the N- and C-terminal domains, respectively, separated by glycosylated bridging domains. Coordinates are in the Protein Data Bank
Original languageEnglish
Pages (from-to)5166-5174
Number of pages9
JournalThe EMBO Journal
Volume18
Issue number19
DOIs
Publication statusPublished - 1999

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