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Adhesion mechanism of human β 2 ‐glycoprotein I to phospholipids based on its crystal structure
Author(s) -
Bouma Barend,
de Groot Philip G.,
van den Elsen Jean M.H.,
Ravelli Raimond B.G.,
Schouten Arie,
Simmelink Marleen J.A.,
Derksen Ronald H.W.M.,
Kroon Jan,
Gros Piet
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.19.5166
Subject(s) - center (category theory) , library science , theology , chemistry , philosophy , crystallography , computer science
Human β 2 ‐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 β 2 ‐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 (accession No. 1QUB).