1GWB

STRUCTURE OF GLYCOPROTEIN 1B

Summary for 1GWB

• Entry DOI: 10.2210/pdb1gwb/pdb
• Related: 1K13 1M0Z 1M10
• Descriptor: PLATELET GLYCOPROTEIN IB ALPHA CHAIN, PLATINUM (II) ION, ACETIC ACID, ... (6 entities in total)
• Functional Keywords: transmembrane, glycoprotein, blood clotting, hemostasis, blood coagulation, leucine-rich repeat, cell adhesion, disease mutation, polymorphism, von willebrand disease, bernard soulier syndrome
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Membrane; Single-pass type I membrane protein: P07359
• Total number of polymer chains: 2
• Total formula weight: 64630.04

Authors

Emsley, J.,Uff, S.,Clemetson, K.J.M.,Clemetson, J.M.,Harrison, T. (deposition date: 2002-03-14, release date: 2003-02-06, Last modification date: 2020-07-29)

Primary citation

Uff, S.,Clemetson, J.M.,Harrison, T.,Clemetson, K.J.,Emsley, J.
Crystal Structure of the Platelet Glycoprotein Ib-Alpha N-Terminal Domain Reveals an Unmasking Mechanism of Receptor Activation
J.Biol.Chem., 277:35657-, 2002

PubMed Abstract: 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.

PubMed: 12087105
DOI: 10.1074/JBC.M205271200

Experimental method

X-RAY DIFFRACTION (2.8 Å)