NMR and X-RAY structures of human E2-like ubiquitin-fold modifier conjugating enzyme 1 (UFC1) reveal structural and functional conservation in the metazoan UFM1-UBA5-UFC1 ubiquination pathway

Gaohua Liu, Farhad Forouhar, Alexander Eletsky, Hanudatta S. Atreya, James M. Aramini, Rong Xiao, Yuanpeng J. Huang, Mariam Abashidze, Jayaraman Seetharaman, Jinfeng Liu, Burkhard Rost, Thomas Acton, Gaetano T. Montelione, John F. Hunt, Thomas Szyperski

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

For cell regulation, E2-like ubiquitin-fold modifier conjugating enzyme 1 (Ufc1) is involved in the transfer of ubiquitin-fold modifier 1 (Ufm1), a ubiquitin like protein which is activated by E1-like enzyme Uba5, to various target proteins. Thereby, Ufc1 participates in the very recently discovered Ufm1-Uba5-Ufc1 ubiquination pathway which is found in metazoan organisms. The structure of human Ufc1 was solved by using both NMR spectroscopy and X-ray crystallography. The complementary insights obtained with the two techniques provided a unique basis for understanding the function of Ufc1 at atomic resolution. The Ufc1 structure consists of the catalytic core domain conserved in all E2-like enzymes and an additional N-terminal helix. The active site Cys116, which forms a thio-ester bond with Ufm1, is located in a flexible loop that is highly solvent accessible. Based on the Ufc1 and Ufm1 NMR structures, a model could be derived for the Ufc1-Ufm1 complex in which the C-terminal Gly83 of Ufm1 may well form the expected thio-ester with Cys116, suggesting that Ufm1-Ufc1 functions as described for other E1-E2-E3 machineries. α-helix 1 of Ufc1 adopts different conformations in the crystal and in solution, suggesting that this helix plays a key role to mediate specificity.

Original languageEnglish (US)
Pages (from-to)127-136
Number of pages10
JournalJournal of Structural and Functional Genomics
Volume10
Issue number2
DOIs
StatePublished - Apr 2009

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Genetics

Keywords

  • E2
  • Ubiquitin
  • Ubiquitin conjugating enzyme
  • Ufc1
  • Ufm1

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