Publication Date:
2002-08-17
Description:
Transient interactions of platelet-receptor glycoprotein Ibalpha (GpIbalpha) and the plasma protein von Willebrand factor (VWF) reduce platelet velocity at sites of vascular damage and play a role in haemostasis and thrombosis. Here we present structures of the GpIbalpha amino-terminal domain and its complex with the VWF domain A1. In the complex, GpIbalpha wraps around one side of A1, providing two contact areas bridged by an area of solvated charge interaction. The structures explain the effects of gain-of-function mutations related to bleeding disorders and provide a model for shear-induced activation. These detailed insights into the initial interactions in platelet adhesion are relevant to the development of antithrombotic drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huizinga, Eric G -- Tsuji, Shizuko -- Romijn, Roland A P -- Schiphorst, Marion E -- de Groot, Philip G -- Sixma, Jan J -- Gros, Piet -- New York, N.Y. -- Science. 2002 Aug 16;297(5584):1176-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, Netherlands. e.g.huizinga@chem.uu.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12183630" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Substitution
;
Bernard-Soulier Syndrome/genetics/metabolism
;
Binding Sites
;
Blood Platelets/metabolism/physiology
;
Crystallization
;
Crystallography, X-Ray
;
Humans
;
Hydrogen Bonding
;
Ligands
;
Models, Molecular
;
Mutation
;
Platelet Adhesiveness
;
Platelet Glycoprotein GPIb-IX Complex/*chemistry/genetics/*metabolism
;
Protein Conformation
;
Protein Structure, Quaternary
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Recombinant Proteins/chemistry/metabolism
;
Repetitive Sequences, Amino Acid
;
Static Electricity
;
von Willebrand Diseases/genetics/metabolism
;
von Willebrand Factor/*chemistry/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
