Glycoprotein Ib-IX-V complex

[1] It primarily functions to mediate the first critical step in platelet adhesion, by facilitating binding to von Willebrand factor (VWF) on damaged sub-endothelium under conditions of high fluid shear stress.

GPIb-IX-V offers a critical role in thrombosis, metastasis, and the life cycle of platelets, and is implicated in a number of thrombotic pathological processes such as stroke or myocardial infarction.

[1] Each of the four subunits (GPIbα, GPIbβ, GPIX and GPV) is part of the leucine rich repeat motif superfamily.

This parallel β-coil region is made up of three sided coils stacked in layers and contains two asparagine residues (Asn21 and Asn159), which serve as N-glycosylation sites.

In the extracellular domain (ectodomain), both the N-capping and C-capping regions, which flank the leucine rich repeat sequence, contain two interlocking disulfide bonds.

GPIbβ contains only one N-glycosylation site (Asn41) and is disulfide linked to GPIbα immediately proximal to the plasma membrane of the platelet via Cys122 located at the junction of the extracellular and transmembrane domains.

The region adjacent to the membrane is enriched in basic residues and Ser166 found more distally is phosphorylated and appears to have a role in platelet cytoskeletal rearrangement.

There have been a number of mutations associated with BSS patients that have been mapped to GPIbα, GPIbβ and GPIX demonstrating that all three subunits are required for effective surface expression of the complex on platelets.

View from the top of the membrane proximal portion of GPIb-IX indicating in red the disulfide bonds between GPIbα and GPIbβ.
A ribbon diagram depicting the crystal structure of the GPIbα N-terminal domain including the VWF A1 and thrombin binding sites.
A ribbon diagram depicting the various components of the GPIbα subunit.
A ribbon diagram depicting the crystal structure of the GPIbβ extracellular domain . The N-terminus is positioned at the top, the concave β-strands sit to the right and the convex loops are positioned to the left. Disulfide bonds present in LRR regions are indicated in yellow.
Interaction of GPV with GPIb-IX via transmembrane (TM) domains. The image demonstrates the accessibility of the GPIbα transmembrane helix for direct association with the GPV transmembrane helix as well as the inaccessibility of the GPIX transmembrane helix.