WHO.

SummaryThe 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.

Since the initial discovery of the endosomal sorting complex required for transport (ESCRT) pathway, research in this field has exploded. ESCRT proteins are part of the endosomal trafficking system and play a crucial role in the biogenesis of multivesicular bodies by functioning in the formation of vesicles that bud away from the cytoplasm. Subsequently, a surprising role for ESCRT proteins was defined in the budding step of some enveloped retroviruses, including HIV-1. ESCRT proteins are also employed in this outward budding process, which results in the resolution of a membranous tether between the host cell and the budding virus particle. Remarkably, it has recently been described that ESCRT proteins also have a role in the topologically equivalent process of cell division. In the same way that viral particles recruit the ESCRT proteins to the site of viral budding, ESCRT proteins are also recruited to the midbody – the site of release of daughter cell from mother cell during cytokinesis. In this Commentary, we describe recent advances in the understanding of ESCRT proteins and how they act to mediate these diverse processes.