J. H. Morrissey, V. Pureza, R. L. Davis-Harrison, S. G. Sligar, C. M. Rienstra,
A. Z. Kijac, Y. Z. Ohkubo, and E. Tajkhorshid.
Protein membrane interactions: blood clotting on nanoscale bilayer.
Journal of Thrombosis and Haemostasis, 7:169-172, 2009.
MORR2009-ET
The clotting cascade requires the assembly of protease–cofactor complexes on
membranes with exposed anionic phospholipids. Despite their importance, protein–
membrane interactions in clotting remain relatively poorly understood. Calcium ions are
known to induce anionic phospholipids to cluster, and we propose that clotting proteins
assemble preferentially on such anionic lipid-rich microdomains. Until recently, there was
no way to control the partitioning of clotting proteins into or out of specific membrane
microdomains, so experimenters only knew the average contributions of phospholipids to
blood clotting. The development of nanoscale membrane bilayers (Nanodiscs) has now
allowed us to probe, with nanometer resolution, how local variations in phospholipid
composition regulate the activity of key protease–cofactor complexes in blood clotting.
Furthermore, exciting new progress in solid-state NMR and large-scale molecular
dynamics simulations allow structural insights into interactions between proteins and
membrane surfaces with atomic resolution.
