The β20-β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions

Alon Herschhorn, Christopher Gu, Francesca Moraca, Xiaochu Ma, Mark Farrell, Amos B. Smith, Marie Pancera, Peter D. Kwong, Arne Schön, Ernesto Freire, Cameron Abrams, Scott C. Blanchard, Walther Mothes, Joseph G. Sodroski

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally "closed" State 1 to more "open" conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control switch for Env structural rearrangements. We identify the gp120 β20-β21 element as a major regulator of Env transitions. Several amino acid changes in the β20-β21 base lead to open Env conformations, recapitulating the structural changes induced by CD4 binding. These HIV-1 mutants require less CD4 to infect cells and are relatively resistant to State 1-preferring broadly neutralizing antibodies. These data provide insights into the molecular mechanism and vulnerability of HIV-1 entry.

Original languageEnglish (US)
Article number1049
JournalNature communications
Issue number1
StatePublished - Dec 1 2017

Bibliographical note

Funding Information:
We thank E. Carpelan for manuscript preparation; the AIDS Research and the Reference Reagent Program, Division of AIDS, NIAID, NIH for providing the following anti-HIV-1 Env antibodies: VRC01, VRC03, 3BNC117, F105, 10-1074, 10E8, 4E10, 7H6, and 35O22, the psPAX2 plasmid and T20. We also thank Drs. D. Easterhoff, T. Bradley, and B. Haynes for providing the 902090 expression plasmids, Dr. J. Robinson (Tulane University) for the 17b and 19b expression plasmids, Dr. J. Mascola for the VRC34 expression plasmids and Dr. X.-P. Kong for the 830 A Fab. A.H. is the recipient of an amfAR Mathilde Krim Fellowship in Basic Biomedical Research (108501-53-RKNT) and was also supported by a Phase II amfAR research grant 109285-58-RKVA for independent investigators. Support for this work was also provided by grants from the NIH to J.G.S. (grants AI24755, AI124982, P01 GM56550, and AI100645), W.M. (grants GM116654 and P01 GM56550), A.B.S. (P01 GM 56550) and S.C.B. (grant GM098859).

Fingerprint Dive into the research topics of 'The β20-β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions'. Together they form a unique fingerprint.

Cite this