1FNS

CRYSTAL STRUCTURE OF THE VON WILLEBRAND FACTOR (VWF) A1 DOMAIN I546V MUTANT IN COMPLEX WITH THE FUNCTION BLOCKING FAB NMC4

Summary for 1FNS

• Entry DOI: 10.2210/pdb1fns/pdb
• Descriptor: IMMUNOGLOBULIN NMC-4 IGG1, VON WILLEBRAND FACTOR, ... (4 entities in total)
• Functional Keywords: von willebrand factor, glycoprotein iba (a:alpha) binding, complex (willebrand-immunoglobulin), blood coagulation type 2b von willebrand disease, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P04275
• Total number of polymer chains: 3
• Total formula weight: 70230.02

Authors

Varughese, K.I. (deposition date: 2000-08-23, release date: 2000-10-18, Last modification date: 2024-10-16)

Primary citation

Celikel, R.,Ruggeri, Z.M.,Varughese, K.I.
von Willebrand factor conformation and adhesive function is modulated by an internalized water molecule.
Nat.Struct.Biol., 7:881-884, 2000

PubMed Abstract: Platelet participation in hemostasis and arterial thrombosis requires the binding of glycoprotein (GP) Ibalpha to von Willebrand factor (vWF). Hemodynamic forces enhance this interaction, an effect mimicked by the substitution I546V in the vWF A1 domain. A water molecule becomes internalized near the deleted Ile methyl group. The change in hydrophobicity of the local environment causes positional changes propagated over a distance of 27 A. As a consequence, a major reorientation of a peptide plane occurs in a surface loop involved in GP Ibalpha binding. This distinct vWF conformation shows increased platelet adhesion and provides a structural model for the initial regulation of thrombus formation.

PubMed: 11017197
DOI: 10.1038/79639

Experimental method

X-RAY DIFFRACTION (2 Å)