Tsg101 chaperone function revealed by HIV-1 assembly inhibitors

Madeleine Strickland, Lorna S. Ehrlich, Susan Watanabe, Mahfuz Khan, Marie Paule Strub, Chi Hao Luan, Michael D. Powell, Jonathan Leis, Nico Tjandra*, Carol A. Carter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


HIV-1 replication requires Tsg101, a component of cellular endosomal sorting complex required for transport (ESCRT) machinery. Tsg101 possesses an ubiquitin (Ub) E2 variant (UEV) domain with a pocket that can bind PT/SAP motifs and another pocket that can bind Ub. The PTAP motif in the viral structural precursor polyprotein, Gag, allows the recruitment of Tsg101 and other ESCRTs to virus assembly sites where they mediate budding. It is not known how or even whether the UEV Ub binding function contributes to virus production. Here, we report that disruption of UEV Ub binding by commonly used drugs arrests assembly at an early step distinct from the late stage involving PTAP binding disruption. NMR reveals that the drugs form a covalent adduct near the Ub-binding pocket leading to the disruption of Ub, but not PTAP binding. We conclude that the Ub-binding pocket has a chaperone function involved in bud initiation.

Original languageEnglish (US)
Article number1391
JournalNature Communications
Issue number1
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


Dive into the research topics of 'Tsg101 chaperone function revealed by HIV-1 assembly inhibitors'. Together they form a unique fingerprint.

Cite this