title: Atomic resolution view into the structure-function relationships of the human myelin peripheral membrane protein P2.
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.
authors.affiliation: Department of Biochemistry, University of Oulu, Oulu, Finland.
authors.forename: Salla
authors.initials: S
authors.lastname: Ruskamo
authors.affiliation: Molecular Biology Unit, Institute of Medical Sciences (IMS), Banaras Hindu University, Varanasi, India.
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Yadav
authors.affiliation: Department of Biochemistry, University of Oulu, Oulu, Finland.
authors.forename: Satyan
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, University of Oulu, Oulu, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Lehtimäki
authors.affiliation: Department of Biochemistry, University of Oulu, Oulu, Finland.
authors.forename: Saara
authors.initials: S
authors.lastname: Laulumaa
authors.affiliation: Max Planck Institute for Experimental Medicine, Göttingen, Germany.
authors.forename: Shweta
authors.initials: S
authors.lastname: Aggarwal
authors.affiliation: Max Planck Institute for Experimental Medicine, Göttingen, Germany.
authors.forename: Mikael
authors.initials: M
authors.lastname: Simons
authors.affiliation: Institute of Biological Interfaces (IBG-2), Karlsruhe Institute for Technology (KIT), Karlsruhe, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Bürck
authors.affiliation: Institute of Biological Interfaces (IBG-2), Karlsruhe Institute for Technology (KIT), Karlsruhe, Germany.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.affiliation: Department of Biochemistry, University of Oulu, Oulu, Finland.
authors.forename: André H
authors.initials: AH
authors.lastname: Juffer
authors.affiliation: Department of Biochemistry, University of Oulu, Oulu, Finland.
authors.forename: Inari
authors.initials: I
authors.lastname: Kursula
authors.affiliation: Department of Biochemistry, University of Oulu, Oulu, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Kursula
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018996:Myelin P2 Protein / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D018996:Myelin P2 Protein
keywords: human myelin peripheral membrane protein P2; membrane proteins; myelin