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. 2021 Sep 13;17(10):1075–1083. doi: 10.1038/s41589-021-00858-8

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a, ARIH2 schematic color-coded by domains. The catalytic Cys310 (cat Cys) in the Rcat domain is indicated with a yellow star. Nter, N terminus. b, Crystal structure of autoinhibited ARIH2 (residues 51–493) is shown in center, with domains colored as in a, zinc atoms as spheres and Ariadne domain helices numbered. The ARIH2 UBAL, RING1, RTI helix and IBR domains form an E2~UB-binding platform. Left inset, UBE2L3~UB (from complex with neddylated CRL1-bound ARIH1, ref. ²³) modeled onto the ARIH2 E2~UB-binding platform. Right inset, close-up (rotated 30° in x and 30° in y) highlighting L381, E382 and E455 mediating autoinhibition. ARIH2 catalytic Cys thiol is shown as a yellow sphere. c, Color-coded schematics of subunits and domains of neddylated CRL5^Vif-CBFβ and APOBEC3C (A3C). d, Model of ARIH2* (full-length ARIH2 with L381A, E382A and E455A residue substitutions) complex with neddylated CRL5^Vif-CBFβ and A3C in cryo-EM reconstruction low-pass filtered to 7.5 Å. Coordinates for ARIH2*, RBX2 and a portion of neddylated CUL5 (CR3 domain through the C terminus) were built into the map shown in Extended Data Fig. 2b. Structures of A3C³⁹ and Vif-CBFβ-ELOBC-CUL5 N-terminal domain³⁶ were fit in density.