Molecular dynamics studies of the transmembrane domain of gp41 from HIV-1.
Helix-helix interactions in the putative three-helix bundle formation of the gp41 transmembrane (TM) domain may contribute to the process of virus-cell membrane fusion in HIV-1 infection. In this study, molecular dynamics is used to analyze and compare the conformations of monomeric and trimeric forms of the TM domain in various solvent systems over the course of 4 to 23-ns simulations. The trimeric bundles of the TM domain were stable as helices and remained associated in a hydrated POPE lipid bilayer for the duration of the 23-ns simulation. Several stable inter-chain hydrogen bonds, mostly among the three deprotonated arginine residues located at the center of each of the three TM domains, formed in a right-handed bundle embedded in the lipid bilayer. No such bonds were observed when the bundle was left-handed or when the central arginine residue in each of the three TM helices was replaced with isoleucine (R_I mutant), suggesting that the central arginine residues may play an essential role in maintaining the integrity of the three-helix bundle. These observations suggest that formation of the three-helix bundle of the TM domain may play a role in the trimerization of gp41, thought to occur during the virus-cell membrane fusion process.
Kim
Jong Hwa
JH
Department of Chemistry, Alabama A&M University, Normal, AL 35762, USA. jong.kim@aamu.edu
Hartley
Taryn L
TL
Curran
A Rachael
AR
Engelman
Donald M
DM
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001120:Arginine / Q000737:chemistry; D003198:Computer Simulation; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000235:genetics; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D055550:Protein Stability; D017434:Protein Structure, Tertiary
D015700:HIV Envelope Protein gp41; D001120:Arginine