Xueqing Wang, Alexandre Slater, Sarah C Lee, Neale Harrison, Naomi L Pollock, Saskia E Bakker, Stefano Navarro, Bernhard Nieswandt, Tim R Dafforn, Ángel García, Steve P Watson, Michael G Tomlinson
The collagen/fibrin(ogen) receptor, glycoprotein VI (GPVI), is a platelet activating receptor and a promising anti-thrombotic drug target. However, while agonist-induced GPVI clustering on platelet membranes has been shown to be essential for its activation, it is unknown if GPVI dimerisation represents a unique conformation for ligand binding. Current GPVI structures all contain only the two immunoglobulin superfamily (IgSF) domains in the GPVI extracellular region, so lacking the mucin-like stalk, transmembrane, cytoplasmic tail of GPVI and its associated Fc receptor γ (FcRγ) homodimer signalling chain, and provide contradictory insights into the mechanisms of GPVI dimerisation...
February 21, 2024: Archives of Biochemistry and Biophysics