Quaternary organization of GPIb-IX complex and insights into Bernard-Soulier syndrome revealed by the structures of GPIbβ and a GPIbβ/GPIX chimera.

ABSTRACT: Platelet GPIb-IX receptor complex has 3 subunits GPIbα, GPIbβ, and GPIX, which assemble with a ratio of 1:2:1. Dysfunction in surface expression of the complex leads to Bernard-Soulier syndrome. We have crystallized the GPIbβ ectodomain (GPIbβ(E)) and determined the structure to show a single leucine-rich repeat with N- and C-terminal disulphide-bonded capping regions. The structure of a chimera of GPIbβ(E) and 3 loops (a,b,c) taken from the GPIX ectodomain sequence was also determined. The chimera (GPIbβ(Eabc)), but not GPIbβ(E), forms a tetramer in the crystal, showing a quaternary interface between GPIbβ and GPIX. Central to this interface is residue Tyr106 from GPIbβ, which inserts into a pocket generated by 2 loops (b,c) from GPIX. Mutagenesis studies confirmed this interface as a val

SUBMITTER: McEwan PA 

PROVIDER: S-EPMC3217411 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature