Structure of a Novel Shoulder-to-Shoulder p24 Dimer in Complex with the Broad-Spectrum Antibody A10F9 and Its Implication in Capsid Assembly

Gu, Ying; Cao, Fang; Wang, Lei; Hou, Wangheng; Zhang, Jun; Hew, Choy-leong; Li, Shaowei; Yuan, Y. Adam; Xia, Ningshao

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Structure of a Novel Shoulder-to-Shoulder p24 Dimer in Complex with the Broad-Spectrum Antibody A10F9 and Its Implication in Capsid Assembly

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Apr 19 2013
By Gu, Ying ; Cao, Fang ; Wang, Lei ; ...

File Language:

English

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Alternative Title:

PLoS One
Personal Author:

Gu, Ying ; Cao, Fang ; Wang, Lei ; Hou, Wangheng ; Zhang, Jun ; Hew, Choy-leong ; Li, Shaowei ; Yuan, Y. Adam ; Xia, Ningshao
Description:

Mature HIV-1 viral particles assemble as a fullerene configuration comprising p24 capsid hexamers, pentamers and dimers. In this paper, we report the X-ray crystal structures of the p24 protein from natural HIV-1 strain (BMJ4) in complex with Fab A10F9, which recognizes a conserved epitope in the C-terminal domain of the BMJ4 p24 protein. Our structures reveal a novel shoulder-to-shoulder p24 dimerization mode that is mediated by an S-S bridge at C177. Consistent with these structures, the shoulder-to-shoulder dimer that was obtained from the BMJ4 strain was also observed in p24 proteins from other strains by the introduction of a cysteine residue at position 177. The potential biological significance was further validated by the introduction of a C177A mutation in the BMJ4 strain, which then displays a low infectivity. Our data suggest that this novel shoulder-to-shoulder dimer interface trapped by this unique S-S bridge could represent a physiologically relevant mode of HIV-1 capsid assembly during virus maturation, although Cys residue itself may not be critical for HIV-I replication.
Subjects:

Amino Acid Sequence Antibodies, Monoclonal Capsid Crystallography, X-Ray HIV-1 HIV Antibodies HIV Core Protein P24 Humans Immunoglobulin Fab Fragments Magnetic Resonance Spectroscopy Models, Molecular Molecular Sequence Data Protein Binding Protein Multimerization Protein Structure, Tertiary Solutions Virus Assembly
Source:

PLoS One. 2013; 8(4).
Document Type:

Journal Article
Volume:

8
Issue:

4
Collection(s):

CDC Public Access
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urn:sha256:8e707f67d7a0f0a89965b62a1c49b13f663b4fdcdd027782a7f5edc50daf797c
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https://stacks.cdc.gov/view/cdc/13453/cdc_13453_DS1.pdf
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[PDF - 6.29 MB ]

File Language:

English

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