Intermediate open state of CD4-bound HIV-1 env heterotrimers in asia CRFs.

Autor: Li D; School of basic medical Sciences, Capital Medical University, 10 Xitoutiao You'anMen Street, Beijing, 100069, China; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Guangming District, Shenzhen, 518132, China., Liu L; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Guangming District, Shenzhen, 518132, China; Joint Laboratory for Infectious Disease Prevention and Control, Hygienic Section of Longhua Center for Disease Control and Prevention, Longhua District, Shenzhen, 518109, China., Ye X; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Guangming District, Shenzhen, 518132, China., Chen Y; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Guangming District, Shenzhen, 518132, China., Ren Q; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Guangming District, Shenzhen, 518132, China., Xu S; Joint Laboratory for Infectious Disease Prevention and Control, Hygienic Section of Longhua Center for Disease Control and Prevention, Longhua District, Shenzhen, 518109, China., Ren Y; Joint Laboratory for Infectious Disease Prevention and Control, Hygienic Section of Longhua Center for Disease Control and Prevention, Longhua District, Shenzhen, 518109, China., Cao H; Joint Laboratory for Infectious Disease Prevention and Control, Hygienic Section of Longhua Center for Disease Control and Prevention, Longhua District, Shenzhen, 518109, China. Electronic address: 27392763@qq.com., Wang T; Institute of Infectious Diseases, Shenzhen Bay Laboratory, Guangming District, Shenzhen, 518132, China; Joint Laboratory for Infectious Disease Prevention and Control, Hygienic Section of Longhua Center for Disease Control and Prevention, Longhua District, Shenzhen, 518109, China; Key Laboratory of Computational Chemistry and Drug Design, Peking University Shenzhen Graduate School, Nanshan District, Shenzhen, 518055, China. Electronic address: tau@pku.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Sep 17; Vol. 725, pp. 150249. Date of Electronic Publication: 2024 Jun 13.
DOI: 10.1016/j.bbrc.2024.150249
Abstrakt: The HIV-1 envelope glycoprotein (Env) plays crucial role in viral infection by facilitating viral attachment to host cells and inducing fusion of the virus with the host cell membrane. This fusion allows the HIV-1 viral genome to enter the target cell then triggering various stages of the viral life cycle. The native Env directly interacts with the main receptor CD4 and the co-receptor (CCR5 or CXCR4) in human cell membrane then induces membrane fusion. The elucidation of the structure of Env with CD4 and co-receptors in different HIV-1 subtypes is essential for the understanding of the mechanism of virus entry. Here we report the Cryo-EM structure of the CD4-bound HIV-1 heterotrimeric Env from Asia prevalent CRF07_BC CH119 strain. In this structure, the binding of three CD4 molecules with Env induced extensively conformational changes in gp120, resulting in the transformation of the Env from close state to intermediate open state. Additionally, the conformational shift of V1/V2 loops of the heterotrimeric Env allosterically expose the V3 loop and promoting the further interactions with co-receptor CCR5 or CXCR4. These findings not only illustrate the structural complexity and plasticity of HIV-1 Env but also give new insights how the biological trimeric Env initialize the immune recognition and membrane fusion.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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