Apr 3, 2020

Proteins and Ions Compete for Membrane Interaction: the case of Lactadherin

BioRxiv : the Preprint Server for Biology
A. M. De LioTaras V Pogorelov


Charged molecular species, such as ions, play a vital role in the life of the cell. In particular, divalent calcium ions (Ca2+) are critical for activating cellular membranes. Interactions between Ca2+ and anionic phosphatidylserine (PS) lipids result in structural changes of the plasma membrane and are vital for many signaling pathways, such as the tightly regulated blood coagulation cascade. Upon cell damage, PS lipids are externalized to the outer leaflet, where they are not only exposed to Ca2+, but also to proteins. Lactadherin is a glycoprotein, important for cell- adhesion, that competes with Ca2+ and blood clotting proteins in binding PS lipids, leading to a negative impact on key steps in the coagulation cascade. While a number of experimental studies have been performed on lactadherin's C2 domain's (LactC2) binding affinity for PS molecules, an atomistic description of LactC2 interactions with PS lipids in the plasma membrane is lacking. We performed extensive all-atom sampling and experimental characterization of LactC2-membrane interactions in the presence and absence of Ca2+ and characterized PS-Ca2+ and PS-LactC2 interactions to guide our understanding of how these interactions initiate and impede blood coagulatio...Continue Reading

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