Molecular dynamics studies of the z-z component of the TCR complex in lipid bilayers

The human T-lymphocytes receptor complex consists of the antigenic peptide binding subunit, the heterodimer a-b and the transducing subunit CD3, the latter resulting from the assembly of three dimers: g-d, g-e and z-z. The present work analyses the human z-z homodimer structure in lipid bilayers by Molecular dynamic simulations. We used the palmitoyl-oleoyl-phosphatidylcholine (POPC) that resembles the cell membrane in lipid composition, and the POPC/cholesterol/palmitoyl-sphyngomyelin (1:1:1) that resembles the raft membrane microdomains, thought to be the sites of the signal transducing machinery. Molecular simulations of the z-z structure determined by Call (Cell, 2006) in water, showed the formation of a stable homodimer; the presence of cholesterol and sphyngomyelin produced significant alterations of the structure; water molecules played a crucial role in the arrangement of an interchain hydrogen bonding network; the model in raft showed an a-helix structure more extended (for each chain: 6.3-17.0 Å in POPC and 12.3-27.4 Å in raft), and a more compact packing (the distance between the centers of mass of the two helices was 7.9 Å in raft and 9.7 Å in POPC). Our results suggest a specific conformation of z-z in the raft environment.