PDBsum entry 1k15

Blood clotting

PDB id: 1k15

Contents

Protein chain

165 a.a.

Theoretical model

PDB id:

1k15

Name:

Blood clotting

Title:

Seven tandem leucine-rich repeats of murine glycoprotein 1b alpha

Structure:

Platelet glycoprotein ib-alpha. Chain: a. Fragment: residues 1-165

Source:

Mus musculus. Mouse

Authors:

J.C.Whisstock,Y.Shen,J.A.Lopez,R.K.Andrews,M.C.Berndt

Key ref:

J.C.Whisstock et al. (2002). Molecular modeling of the seven tandem leucine-rich repeats within the ligand-binding region of platelet glycoprotein Ib alpha. Thromb Haemost, 87, 329-333. PubMed id: 11858495

Date:

23-Sep-01 Release date: 10-Apr-02

Protein chain

No UniProt id for this chain

Struc: 165 a.a.

Thromb Haemost 87:329-333 (2002)

PubMed id: 11858495

Molecular modeling of the seven tandem leucine-rich repeats within the ligand-binding region of platelet glycoprotein Ib alpha.

J.C.Whisstock, Y.Shen, J.A.López, R.K.Andrews, M.C.Berndt.

ABSTRACT

Platelet glycoprotein (GP)Ib-IX-V mediates von Willebrand Factor (vWF)-dependent adhesion to vascular subendothelium at high shear in (patho)physiological thrombus formation. The ligand-binding domain of GPIb-IX-V is within the N-terminal 282 residues of GPIb alpha, that contains seven tandem leucine-rich repeats (Leu36-Ala200). Repeats 2-4 are critical for vWF binding. In this study, we have built molecular models of the seven leucine-rich repeats of human, canine and mouse GPIb alpha, providing novel insights into the species-specific interaction between human vWF and its receptor. Interestingly, a major difference between the models was a large negatively charged patch on the concave face of human, but not canine, repeats 2-4. In addition, five individual mutations within the leucine-rich repeats of GPIb alpha associated with the bleeding disorder Bernard-Soulier syndrome, that result in dysfunctional vWF binding, were mapped to the model of human GPIb alpha. This provides the basis for relating these genetic lesions to abnormal function of the receptor.