The structure of the CD3 ¦Æ¦Æ transmembrane dimer in POPC and raft-like lipid bilayer: A molecular dynamics study

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• 作者：Ariel Alcides Petruk ; Sonia Varriale ; Maria Rosaria Coscia ; Lelio Mazzarella ; Antonello Merlino ; Umberto Oreste
• 关键词：CHOL ; cholesterol ; MD ; molecular dynamics ; POPC ; palmitoyl-oleoyl-phosphatidylcholine ; RMSD ; root mean square deviation ; RDF ; radial distribution function ; SM ; sphingomyelin ; TCRT ; cell receptor ; TM ; transmembrane
• 刊名：Biochimica et Biophysica Acta (BBA)/Biomembranes
• 出版年：2013
• 出版时间：November, 2013
• 年：2013
• 卷：1828
• 期：11
• 页码：2637-2645
• 全文大小：2186 K

文摘

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 ¦Æ¦Æ 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 ¦Æ¦Æ 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 ¦Æ¦Æ dimer assumes a specific conformation probably necessary to the correct signal transduction.