Atomic resolution view into the structure-function relationships of the human myelin peripheral membrane protein P2

Acta Crystallogr D Biol Crystallogr. 2014 Jan;70(Pt 1):165-76. doi: 10.1107/S1399004713027910. Epub 2013 Dec 31.

Abstract

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.

Keywords: human myelin peripheral membrane protein P2; membrane proteins; myelin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Cell Membrane / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Myelin P2 Protein / chemistry*
  • Myelin P2 Protein / metabolism*
  • Protein Binding
  • Protein Conformation

Substances

  • Myelin P2 Protein

Associated data

  • PDB/4BVM