Structural and functional analysis of a novel interaction motif within UFM1-activating enzyme 5 (UBA5) required for binding to ubiquitin-like proteins and ufmylation

Sabrina Habisov, Jessica Huber, Yoshinobu Ichimura, Masato Akutsu, Natalia Rogova, Frank Loehr, David G. McEwan, Terje Johansen, Ivan Dikic, Volker Doetsch, Masaaki Komatsu, Vladimir V. Rogov, Vladimir Kirkin

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

The covalent conjugation of ubiquitin-fold modifier 1 (UFM1) to proteins generates a signal that regulates transcription, response to cell stress, and differentiation. Ufmylation is initiated by ubiquitin-like modifier activating enzyme 5 (UBA5), which activates and transfers UFM1 to ubiquitin-fold modifierconjugating enzyme 1 (UFC1). The details of the interaction between UFM1 and UBA5 required for UFM1 activation and its downstream transfer are however unclear. In this study, we described and characterized a combined linear LC3-interacting region/UFM1-interacting motif (LIR/UFIM) within the C terminus of UBA5. This single motif ensures that UBA5 binds both UFM1 and light chain 3/γ-aminobutyric acid receptor-associated proteins (LC3/GABARAP), two ubiquitin (Ub)-like proteins. We demonstrated that LIR/UFIM is required for the full biological activity of UBA5 and for the effective transfer of UFM1 onto UFC1 and a downstream protein substrate both in vitro and in cells. Taken together, our study provides important structural and functional insights into the interaction between UBA5 and Ub-like modifiers, improving the understanding of the biology of the ufmylation pathway.

Original languageEnglish
Pages (from-to)9025-9041
Number of pages17
JournalJournal of Biological Chemistry
Volume291
Issue number17
DOIs
Publication statusPublished - 2016 Apr 22
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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