Spontaneous rearrangement of the ?20/?21 strands in simulations of unliganded HIV-1 glycoprotein, gp120.

ABSTRACT: Binding of the viral spike drives cell entry and infection by HIV-1 to the cellular CD4 and chemokine receptors with associated conformational change of the viral glycoprotein envelope, gp120. Crystal structures of the CD4-gp120-antibody ternary complex reveal a large internal gp120 cavity formed by three domains-the inner domain, outer domain, and bridging sheet domain-and are capped by CD4 residue Phe43. Several structures of gp120 envelope in complex with various antibodies indicated that the bridging sheet adopts varied conformations. Here, we examine bridging sheet dynamics using a crystal structure of gp120 bound to the F105 antibody exhibiting an open bridging sheet conformation and with an added V3 loop. The two strands of the bridging sheet ?2/?3 and ?20/?21 are dissociated from each other and are directed away from the inner and outer domains. Analysis of molecular dynamics (MD) trajectories indicates that the ?2/?3 and ?20/?21 strands rapidly rearrange to interact with the V3 loop and the inner and outer domains, respectively. Residue N425 on ?20 leads the conformational rearrangement of the ?20/?21 strands by interacting with W112 on the inner domain and F382 on the outer domain. An accompanying shift is observed in the inner domain as helix ?1 exhibits a loss in helicity and pivots away from helix ?5. The two simulations provide a framework for understanding the conformational diversity of the bridging sheet and the propensity of the ?20/?21 strand to refold between the inner and outer domains of gp120, in the absence of a bound ligand.

SUBMITTER: Shrivastava IH 

PROVIDER: S-EPMC3464976 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature