Spontaneous Rearrangement of the β20/β21 Strands in Simulations of Unliganded HIV‑1 Glycoprotein, gp120
mediaposted on 2016-02-20, 10:12 authored by Indira H. Shrivastava, Kaylee Wendel, Judith M. LaLonde
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 domainsthe inner domain, outer domain, and bridging sheet domainand 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 β2/β3 and β20/β21 are dissociated from each other and are directed away from the inner and outer domains. Analysis of molecular dynamics (MD) trajectories indicates that the β2/β3 and β20/β21 strands rapidly rearrange to interact with the V3 loop and the inner and outer domains, respectively. Residue N425 on β20 leads the conformational rearrangement of the β20/β21 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 α1 exhibits a loss in helicity and pivots away from helix α5. The two simulations provide a framework for understanding the conformational diversity of the bridging sheet and the propensity of the β20/β21 strand to refold between the inner and outer domains of gp120, in the absence of a bound ligand.
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gp 120 envelopespike drives cell entrygp 120Residue N 425strandCD 4 residue Phe 43.MDCD 4gp 120. Crystal structuresW 112sheet dynamicsSpontaneous Rearrangementsheet conformationgp 120Bindinghelix α5.F 382helix α1 exhibitsgp 120 cavitycrystal structureF 105 antibodychemokine receptorsHIVglycoprotein envelopeV 3 loop