The HIV-1 Env gp120 Inner Domain Shapes the Phe43 Cavity and the CD4 Binding Site-Reference-Cited by-同舟云学术

The HIV-1 Env gp120 Inner Domain Shapes the Phe43 Cavity and the CD4 Binding Site

Published:2020-06-30 Issue:3 Volume:11 Page:
ISSN:2161-2129
Container-title:mBio
language:en
Short-container-title:mBio

Author:

Prévost Jérémie¹²,Tolbert William D.³,Medjahed Halima¹,Sherburn Rebekah T.³,Madani Navid⁴⁵,Zoubchenok Daria¹²,Gendron-Lepage Gabrielle¹,Gaffney Althea E.⁶,Grenier Melissa C.⁶,Kirk Sharon⁶,Vergara Natasha⁷,Han Changze⁸,Mann Brendan T.⁹¹⁰,Chénine Agnès L.⁹¹⁰,Ahmed Adel⁷,Chaiken Irwin⁷,Kirchhoff Frank¹¹,Hahn Beatrice H.¹²,Haim Hillel⁸,Abrams Cameron F.⁷,Smith Amos B.⁶,Sodroski Joseph⁴⁵,Pazgier Marzena³,Finzi Andrés¹²¹³

Affiliation:

1. Centre de Recherche du CHUM, Montreal, Quebec, Canada

2. Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, Quebec, Canada

3. Infectious Diseases Division, Department of Medicine of Uniformed Services, University of the Health Sciences, Bethesda, Maryland, USA

4. Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

5. Department of Microbiology, Harvard Medical School, Boston, Massachusetts, USA

6. Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA

7. Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

8. Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

9. U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA

10. Henry M. Jackson Foundation for the Advancement of the Military Medicine, Bethesda, Maryland, USA

11. Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany

12. Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

13. Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada

Abstract

The Phe43 cavity of HIV-1 envelope glycoproteins (Env) is an attractive druggable target. New promising compounds, including small CD4 mimetics (CD4mc), were shown to insert deeply into this cavity. Here, we identify a new network of residues that helps to shape this highly conserved CD4 binding pocket and characterize the structural determinants responsible for Env sensitivity to small CD4 mimetics.

Funder

SPP

HHS | National Institutes of Health

HHS | NIH | National Institute of Allergy and Infectious Diseases

Deutsche Forschungsgemeinschaft

Canada Research Chairs

Gouvernement du Canada | Canadian Institutes of Health Research

University of Iowa

Publisher

American Society for Microbiology

Subject

Virology,Microbiology