Browsing by Author "Shweta Aggarwal"

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Atomic resolution view into the structure-function relationships of the human myelin peripheral membrane protein P2
(2014) Salla Ruskamo; Ravi P. Yadav; Satyan Sharma; Mari Lehtimäki; Saara Laulumaa; Shweta Aggarwal; Mikael Simons; Jochen Bürck; Anne S. Ulrich; André H. Juffer; Inari Kursula; Petri Kursula
P2 is a fatty acid-binding protein expressed in vertebrate peripheral nerve myelin, where it may function in bilayer stacking and lipid transport. P2 binds to phospholipid membranes through its positively charged surface and a hydrophobic tip, and accommodates fatty acids inside its barrel structure. The structure of human P2 refined at the ultrahigh resolution of 0.93 Å allows detailed structural analyses, including the full organization of an internal hydrogen-bonding network. The orientation of the bound fatty-acid carboxyl group is linked to the protonation states of two coordinating arginine residues. An anion-binding site in the portal region is suggested to be relevant for membrane interactions and conformational changes. When bound to membrane multilayers, P2 has a preferred orientation and is stabilized, and the repeat distance indicates a single layer of P2 between membranes. Simulations show the formation of a double bilayer in the presence of P2, and in cultured cells wild-type P2 induces membrane-domain formation. Here, the most accurate structural and functional view to date on P2, a major component of peripheral nerve myelin, is presented, showing how it can interact with two membranes simultaneously while going through conformational changes at its portal region enabling ligand transfer. © 2014 International Union of Crystallography.