Reconstitution of the Platelet Glycoprotein Ib-IX Complex in Phospholipid Bilayer Nanodiscs

Chapter 11 - Reconstitution of membrane proteins in phospholipid bilayer nanodiscs.

Self-assembled phospholipid bilayer Nanodiscs have become an important and versatile tool among model membrane systems to functionally reconstitute membrane proteins. Nanodiscs consist of lipid domains encased within an engineered derivative of apolipoprotein A-1 scaffold proteins, which can be tailored to yield homogeneous preparations of disks with different diameters, and with epitope tags f...

Platelet Glycoprotein Ib-IX and Malignancy

Identification of a juxtamembrane mechanosensitive domain in the platelet mechanosensor glycoprotein Ib-IX complex.

How glycoprotein (GP)Ib-IX complex on the platelet surface senses the blood flow through its binding to the plasma protein von Willebrand factor (VWF) and transmits a signal into the platelet remains unclear. Here we show that optical tweezer-controlled pulling of the A1 domain of VWF (VWF-A1) on GPIb-IX captured by its cytoplasmic domain induced unfolding of a hitherto unidentified structural ...

Interaction of calmodulin with the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex.

Engagement of platelet membrane glycoprotein (GP) Ib-IX-V by von Willebrand factor triggers Ca(++)-dependent activation of alphaIIbbeta3, resulting in (patho)physiological thrombus formation. It is demonstrated here that the cytoplasmic domain of GPIb-IX-V associates with cytosolic calmodulin. First, an anti-GPIbalpha antibody coimmunoprecipitated GPIb-IX and calmodulin from platelet lysates. F...

Platelet glycoprotein Ib-IX as a regulator of systemic inflammation.

OBJECTIVE The platelet glycoprotein Ib-IX (GP Ib-IX) receptor is a well-characterized adhesion receptor supporting hemostasis and thrombosis via interactions with von Willebrand factor. We examine the GP Ib-IX/von Willebrand factor axis in murine polymicrobial sepsis, as modeled by cecal ligation and puncture (CLP). APPROACH AND RESULTS Genetic absence of the GP Ib-IX ligand, von Willebrand f...