Issue 3, 2023

Mutation in the D1 domain of CD4 receptor modulates the binding affinity to HIV-1 gp120

Abstract

The gp120 surface subunit of HIV-1 envelope lycoprotein (Env) is the key component for the viral entry process through interaction with the CD4 binding site (CD4bs) of the primary receptor CD4. The point mutant was introduced into SD1, a CD4 D1 variant, to enhance the interaction with HIV-1 gp120.The three-dimensional structures of gp120 and SD1 were determined using homology modeling based on the results previously determined by X-ray crystallography. The binding models were carried out via protein–protein docking tools. The 5 best docking solutions were retained according to the docking scores and were used for structural assessment. Our results demonstrated the consistency between the 3D models of gp120 and SD1 predicted by molecular docking calculations and the co-crystallized data available. We first discovered that most residues in SD1 that interacted with gp120 were located within the region 6–94 of the first N-terminal D1 domain of CD4. SD1 bound to gp120 stably at which 15 residues formed 20 hydrogen bonds with 16 residues of gp120. Five pairs of electrostatic interactions between positively and negatively charged side chains of amino acids were identified in the SD1-gp120 interface, which showed an increased number of electrostatic interactions with gp120. The mutant in the D1 domain of human CD4 receptor could strengthen binding affinity with HIV-1 gp120 and might improve the interaction pattern of the neighboring residues. The sequence analysis of gp120 suggested that Asp186, Asn189, Arg191, Glu293, Phe318 and Tyr319 were located in the variable regions of gp120, which may be HIV-1 AE strain-specific amino acid residues. Together, the results presented in this study contributed to a better understanding of the changes in the interaction between the gp120 protein and the human host CD4 receptor associated with point mutation in the D1 domain. The stabilized derivative of human CD4 D1 should serve as a promising target for therapeutics development in HIV-1 vaccine and viral entry inhibitor and may warrant further investigation.

Graphical abstract: Mutation in the D1 domain of CD4 receptor modulates the binding affinity to HIV-1 gp120

Article information

Article type
Paper
Submitted
20 Okt 2022
Accepted
23 Dez 2022
First published
11 Jan 2023
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2023,13, 2070-2080

Mutation in the D1 domain of CD4 receptor modulates the binding affinity to HIV-1 gp120

J. Shao, G. Liu and G. Lv, RSC Adv., 2023, 13, 2070 DOI: 10.1039/D2RA06628A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements