A mechanism by which binding of the broadly neutralizing antibody b12 unfolds the inner domain α1 helix in an engineered HIV-1 gp120.

ABSTRACT: Using all-atom simulations, we examine the role of the I109C/Q428C disulfide "stitch" in altering the conformational distribution of engineered HIV-1 gp120 core relevant for binding of the broadly neutralizing recombinant antibody b12. In particular, we propose that the I109C/Q428C stitch results in a conformational distribution favoring an unfolded inner-domain α1-helix upon binding of b12. Using targeted molecular dynamics, we show that folded α1 in the b12-bound conformation of gp120 is stable both with and without the stitch, but that with folded α1, the stitch requires an orientation of the β20/β21 sheet that is sterically incompatible with b12 binding. Forcing β20/β21 into the orientation displayed by the b12-bound conformation after folding α1 with the stitch intact results in parti

SUBMITTER: Emileh A 

PROVIDER: S-EPMC3059550 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature