title: 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.
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 Cys(116), 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 Gly(83) of Ufm1 may well form the expected thio-ester with Cys(116), suggesting that Ufm1-Ufc1 functions as described for other E1-E2-E3 machineries. alpha-helix 1 of Ufc1 adopts different conformations in the crystal and in solution, suggesting that this helix plays a key role to mediate specificity.
authors.affiliation: Department of Chemistry, Northeast Structural Genomics Consortium, The State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Gaohua
authors.initials: G
authors.lastname: Liu
authors.forename: Farhad
authors.initials: F
authors.lastname: Forouhar
authors.forename: Alexander
authors.initials: A
authors.lastname: Eletsky
authors.forename: Hanudatta S
authors.initials: HS
authors.lastname: Atreya
authors.forename: James M
authors.initials: JM
authors.lastname: Aramini
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.forename: Yuanpeng J
authors.initials: YJ
authors.lastname: Huang
authors.forename: Mariam
authors.initials: M
authors.lastname: Abashidze
authors.forename: Jayaraman
authors.initials: J
authors.lastname: Seetharaman
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liu
authors.forename: Burkhard
authors.initials: B
authors.lastname: Rost
authors.forename: Thomas
authors.initials: T
authors.lastname: Acton
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
authors.forename: John F
authors.initials: JF
authors.lastname: Hunt
authors.forename: Thomas
authors.initials: T
authors.lastname: Szyperski
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017510:Protein Folding; D044764:Ubiquitin-Activating Enzymes / Q000737:chemistry; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry*; D014452:Ubiquitins / Q000737:chemistry*
chemical_list: C502096:UFC1 protein, human; D014452:Ubiquitins; D044763:Ubiquitin-Conjugating Enzymes; D044764:Ubiquitin-Activating Enzymes