Understanding the structural basis of HIV-1 restriction by the full length double-domain APOBEC3G

Yang, Hanjing; Ito, Fumiaki; Wolfe, Aaron D.; Li, Shuxing; Mohammadzadeh, Nazanin; Love, Robin P.; Yan, Maocai; Zirkle, Brett; Gaba, Amit; Chelico, Linda; Chen, Xiaojiang S.

doi:10.1038/s41467-020-14377-y

Title: Understanding the structural basis of HIV-1 restriction by the full length double-domain APOBEC3G

Journal Article · Fri Jan 31 00:00:00 EST 2020 · Nature Communications

DOI:https://doi.org/10.1038/s41467-020-14377-y· OSTI ID:1763147

^[1]; Ito, Fumiaki ^[1];

^[1]; Li, Shuxing ^[1]; Mohammadzadeh, Nazanin ^[2]; Love, Robin P. ^[2]; Yan, Maocai ^[3]; Zirkle, Brett ^[1];

^[2];

^[1]

Univ. of Southern California, Los Angeles, CA (United States)
Univ. of Saskatchewan, Saskatoon, SK (Canada)
Univ. of Southern California, Los Angeles, CA (United States); Jining Medical Univ., Shandong (China)

APOBEC3G, a member of the double-domain cytidine deaminase (CD) APOBEC, binds RNA to package into virions and restrict HIV-1 through deamination-dependent or deamination-independent inhibition. Mainly due to lack of a full-length double-domain APOBEC structure, it is unknown how CD1/CD2 domains connect and how dimerization/multimerization is linked to RNA binding and virion packaging for HIV-1 restriction. We report rhesus macaque A3G structures that show different inter-domain packing through a short linker and refolding of CD2. The A3G dimer structure has a hydrophobic dimer-interface matching with that of the previously reported CD1 structure. A3G dimerization generates a surface with intensified positive electrostatic potentials (PEP) for RNA binding and dimer stabilization. Unexpectedly, mutating the PEP surface and the hydrophobic interface of A3G does not abolish virion packaging and HIV-1 restriction. The data support a model in which only one RNA-binding mode is critical for virion packaging and restriction of HIV-1 by A3G.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); Canadian Institutes of Health Research (CIHR); USDOE Office of Science (SC)

Grant/Contract Number:: R01 AI150524; PJT162407

OSTI ID:: 1763147

Journal Information:: Nature Communications, Vol. 11, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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