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Title: Atomic resolution view into the structure–function relationships of the human myelin peripheral membrane protein P2

The structure of the human myelin peripheral membrane protein P2 has been refined at 0.93 Å resolution. In combination with functional experiments in vitro, in vivo and in silico, the fine details of the structure–function relationships in P2 are emerging. 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 andmore » 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.« less
Authors:
 [1] ;  [2] ;  [3] ;  [4] ; ;  [1] ;  [2] ;  [1] ;  [2] ;  [4] ; ;  [5] ; ;  [6] ;  [1] ;  [2] ;  [1] ;  [4] ;  [1] ;  [2] more »;  [4] ;  [7] « less
  1. University of Oulu, Oulu (Finland)
  2. (Finland)
  3. Banaras Hindu University, Varanasi (India)
  4. (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany)
  5. Max Planck Institute for Experimental Medicine, Göttingen (Germany)
  6. Karlsruhe Institute for Technology (KIT), Karlsruhe (Germany)
  7. (Germany)
Publication Date:
OSTI Identifier:
22347812
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section D: Biological Crystallography; Journal Volume: 70; Journal Issue: Pt 1; Other Information: PMCID: PMC3919267; PMID: 24419389; PUBLISHER-ID: mh5108; OAI: oai:pubmedcentral.nih.gov:3919267; Copyright (c) Ruskamo et al. 2014; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; ARGININE; ATOMS; BONDING; CONFORMATIONAL CHANGES; GRAIN ORIENTATION; HYDROGEN; IN VITRO; IN VIVO; INTERACTIONS; LAYERS; LIGANDS; MEMBRANE PROTEINS; SIMULATION; SURFACES