Molecular dynamics simulations of the E1/E2 transmembrane domain of the Semliki Forest virus.
Transmembrane (TM) helix-helix interactions are important for virus budding and fusion. We have developed a simulation strategy that reveals the main features of the helical packing between the TM domains of the two glycoproteins E1 and E2 of the alpha-virus Semliki Forest virus and that can be extrapolated to sketch TM helical packing in other alpha-viruses. Molecular dynamics simulations were performed in wild-type and mutant peptides, both isolated and forming E1/E2 complexes. The simulations revealed that the isolated wild-type E1 peptide formed a more flexible helix than the rest of peptides and that the wild-type E1/E2 complex consists of two helices that intimately pack their N-terminals. The residues located at the interhelical interface displayed the typical motif of the left-handed coiled-coils. These were small and medium residues as Gly, Ala, Ser, and Leu, which also had the possibility to form interhelical Calpha-H...O hydrogen bonds. Results from the mutant complexes suggested that correct packing is a compromise between these residues at both E1 and E2 interhelical interfaces. This compromise allowed prediction of E1-E2 contact residues in the TM spanning domain of other alphaviruses even though the sequence identity of E2 peptides is low in this domain.
Caballero-Herrera
Ana
A
Department of Biosciences at Novum, Karolinska Institutet, S-141 57 Huddinge, Sweden.
Nilsson
Lennart
L
D020816:Amino Acid Motifs; D002462:Cell Membrane / Q000378:metabolism*; D020285:Cryoelectron Microscopy; D019281:Dimerization; D006860:Hydrogen Bonding; D008561:Membrane Fusion; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012672:Semliki forest virus / Q000378:metabolism*; D012984:Software
D010455:Peptides