Uff, S; Clemetson, JM; Harrison, T; Clemetson, KJ; Emsley, J (2002). Crystal structure of the platelet glycoprotein Ib(alpha) N-terminal domain reveals an unmasking mechanism for receptor activation. Journal of biological chemistry, 38(277), pp. 35657-63. Bethesda, Md.: American Society for Biochemistry and Molecular Biology 10.1074/jbc.M205271200
Full text not available from this repository. (Request a copy)Glycoprotein Ib (GPIb) is a platelet receptor with a critical role in mediating the arrest of platelets at sites of vascular damage. GPIb binds to the A1 domain of von Willebrand factor (vWF-A1) at high blood shear, initiating platelet adhesion and contributing to the formation of a thrombus. To investigate the molecular basis of GPIb regulation and ligand binding, we have determined the structure of the N-terminal domain of the GPIb(alpha) chain (residues 1-279). This structure is the first determined from the cell adhesion/signaling class of leucine-rich repeat (LRR) proteins and reveals the topology of the characteristic disulfide-bonded flanking regions. The fold consists of an N-terminal beta-hairpin, eight leucine-rich repeats, a disulfide-bonded loop, and a C-terminal anionic region. The structure also demonstrates a novel LRR motif in the form of an M-shaped arrangement of three tandem beta-turns. Negatively charged binding surfaces on the LRR concave face and anionic region indicate two-step binding kinetics to vWF-A1, which can be regulated by an unmasking mechanism involving conformational change of a key loop. Using molecular docking of the GPIb and vWF-A1 crystal structures, we were also able to model the GPIb.vWF-A1 complex.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
UniBE Contributor: |
Clemetson, Kenneth John |
ISSN: |
0021-9258 |
ISBN: |
12087105 |
Publisher: |
American Society for Biochemistry and Molecular Biology |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:52 |
Last Modified: |
05 Dec 2022 14:16 |
Publisher DOI: |
10.1074/jbc.M205271200 |
PubMed ID: |
12087105 |
Web of Science ID: |
000178117000126 |
URI: |
https://boris.unibe.ch/id/eprint/22195 (FactScience: 32244) |
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