title: The structure of the CD3 ζζ transmembrane dimer in POPC and raft-like lipid bilayer: a molecular dynamics study.
abstract: Plasma membrane lipids significantly affect assembly and activity of many signaling networks. The present work is aimed at analyzing, by molecular dynamics simulations, the structure and dynamics of the CD3 ζζ dimer in palmitoyl-oleoyl-phosphatidylcholine bilayer (POPC) and in POPC/cholesterol/sphingomyelin bilayer, which resembles the raft membrane microdomain supposed to be the site of the signal transducing machinery. Both POPC and raft-like environment produce significant alterations in structure and flexibility of the CD3 ζζ with respect to nuclear magnetic resonance (NMR) model: the dimer is more compact, its secondary structure is slightly less ordered, the arrangement of the Asp6 pair, which is important for binding to the Arg residue in the alpha chain of the T cell receptor (TCR), is stabilized by water molecules. Different interactions of charged residues with lipids at the lipid-cytoplasm boundary occur when the two environments are compared. Furthermore, in contrast to what is observed in POPC, in the raft-like environment correlated motions between transmembrane and cytoplasmic regions are observed. Altogether the data suggest that when the TCR complex resides in the raft domains, the CD3 ζζ dimer assumes a specific conformation probably necessary to the correct signal transduction.
authors.affiliation: Instituto Superior de Investigaciones Biológicas (INSIBIO-CONICET), Chacabuco 461, S. M. de Tucumán, Tucumán T4000ILI, Argentina.
authors.forename: Ariel Alcides
authors.initials: AA
authors.lastname: Petruk
authors.forename: Sonia
authors.initials: S
authors.lastname: Varriale
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Coscia
authors.forename: Lelio
authors.initials: L
authors.lastname: Mazzarella
authors.forename: Antonello
authors.initials: A
authors.lastname: Merlino
authors.forename: Umberto
authors.initials: U
authors.lastname: Oreste
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D000595:Amino Acid Sequence; D017252:CD3 Complex / Q000737:chemistry*; D019281:Dimerization; D008051:Lipid Bilayers / Q000737:chemistry*; D021962:Membrane Microdomains / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D017252:CD3 Complex; D008051:Lipid Bilayers; D015060:1,2-Dipalmitoylphosphatidylcholine; C033036:1-palmitoyl-2-palmitoleoyl-sn-glycero-3-phosphocholine
keywords: CD3 ζζ; CHOL; Lipid raft; MD; Membrane protein; Molecular dynamics; POPC; RDF; RMSD; SM; TCRT; TM; Transmembrane helix; cell receptor; cholesterol; molecular dynamics; palmitoyl-oleoyl-phosphatidylcholine; radial distribution function; root mean square deviation; sphingomyelin; transmembrane