Divergent interfaces and convergent outcome in the structural basis of HIV-2 Vif antagonism of APOBEC3H
Abstract
Primate lentiviruses counteract antiviral APOBEC3 (A3) cytidine deaminases through virion infectivity factor (Vif), which recruits A3 proteins to a Cullin–RING E3 ubiquitin ligase for proteasomal degradation. While HIV-1 Vif is well characterized, HIV-2 Vif remains poorly defined due to divergent sequences. Here we report a 3.08 Å cryo-EM structure of HIV-2 Vif bound to chimpanzee A3H (cpzA3H) and E3 ligase components. HIV-2 Vif adopts a conserved global fold but engages cpzA3H through a binding interface distinct from HIV-1 Vif, achieving target recognition through numerous weak contacts distributed across an extended interface. The structure reveals a direct CBFβ–cpzA3H interface absent in HIV-1 Vif-A3H complexes, establishing CBFβ as a bivalent adaptor that actively contributes to substrate recruitment. Despite these structural differences, lysine 50 of cpzA3H is the shared ubiquitination target of both HIV-1- and HIV-2 Vif-induced degradation, revealing convergent function achieved through divergent structural solutions.
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BibTeX
@article{skorupka2026divergent,
title = {{Divergent interfaces and convergent outcome in the structural basis of HIV-2 Vif antagonism of APOBEC3H}},
author = {Katarzyna A. Skorupka and Kazuhiro Matsuoka and Mayumi Imahashi and Yoshiyuki Yokomaku and Yasumasa Iwatani and Hiroshi Matsuo},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78197-2},
url = {https://www.nature.com/articles/s41467-026-78197-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Divergent interfaces and convergent outcome in the structural basis of HIV-2 Vif antagonism of APOBEC3H
AU - Katarzyna A. Skorupka
AU - Kazuhiro Matsuoka
AU - Mayumi Imahashi
AU - Yoshiyuki Yokomaku
AU - Yasumasa Iwatani
AU - Hiroshi Matsuo
PY - 2026
DA - 2026/10/07
JO - Nature Communications
DO - 10.1038/s41467-026-78197-2
UR - https://www.nature.com/articles/s41467-026-78197-2
AB - Primate lentiviruses counteract antiviral APOBEC3 (A3) cytidine deaminases through virion infectivity factor (Vif), which recruits A3 proteins to a Cullin–RING E3 ubiquitin ligase for proteasomal degradation. While HIV-1 Vif is well characterized, HIV-2 Vif remains poorly defined due to divergent sequences. Here we report a 3.08 Å cryo-EM structure of HIV-2 Vif bound to chimpanzee A3H (cpzA3H) and E3 ligase components. HIV-2 Vif adopts a conserved global fold but engages cpzA3H through a binding interface distinct from HIV-1 Vif, achieving target recognition through numerous weak contacts distributed across an extended interface. The structure reveals a direct CBFβ–cpzA3H interface absent in HIV-1 Vif-A3H complexes, establishing CBFβ as a bivalent adaptor that actively contributes to substrate recruitment. Despite these structural differences, lysine 50 of cpzA3H is the shared ubiquitination target of both HIV-1- and HIV-2 Vif-induced degradation, revealing convergent function achieved through divergent structural solutions.
SN - 2041-1723
ER -