The UBAP1 Subunit of ESCRT-I Interacts with Ubiquitin via a SOUBA Domain

TLDR

ESCRTs mediate endosomal sorting of ubiquitinated cargo, multivesicular body biogenesis, late cytokinesis, and retroviral budding. We found that UBAP1, a subunit of human ESCRT‑I, forms a stable 1:1:1:1 complex with Vps23/TSG101, VPS28, and VPS37, and its C‑terminal SOUBA domain contains three ubiquitin‑binding UBAs that are required for ESCRT‑I–mediated degradation of antiviral surface proteins such as tetherin by viral proteins Vpu and K5.

Abstract

The endosomal sorting complexes required for transport (ESCRTs) facilitate endosomal sorting of ubiquitinated cargo, MVB biogenesis, late stages of cytokinesis, and retroviral budding. Here we show that ubiquitin associated protein 1 (UBAP1), a subunit of human ESCRT-I, coassembles in a stable 1:1:1:1 complex with Vps23/TSG101, VPS28, and VPS37. The X-ray crystal structure of the C-terminal region of UBAP1 reveals a domain that we describe as a solenoid of overlapping UBAs (SOUBA). NMR analysis shows that each of the three rigidly arranged overlapping UBAs making up the SOUBA interact with ubiquitin. We demonstrate that UBAP1-containing ESCRT-I is essential for degradation of antiviral cell-surface proteins, such as tetherin (BST-2/CD317), by viral countermeasures, namely, the HIV-1 accessory protein Vpu and the Kaposi sarcoma-associated herpesvirus (KSHV) ubiquitin ligase K5.