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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. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Liu, G, Forouhar, F, Eletsky, A, Atreya, HS, Aramini, JM, Xiao, R, Huang, YJ, Abashidze, M, Seetharaman, J, Liu, J, Rost, B, Acton, T, Montelione, GT, Hunt, JF, Szyperski, T |
Journal | J Struct Funct Genomics |
Volume | 10 |
Issue | 2 |
Pagination | 127-36 |
Date Published | 2009 Apr |
ISSN | 1570-0267 |
Keywords | Animals, Crystallography, X-Ray, Humans, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular, Protein Conformation, Protein Folding, Ubiquitin-Activating Enzymes, Ubiquitin-Conjugating Enzymes, Ubiquitins |
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. |
DOI | 10.1007/s10969-008-9054-7 |
Alternate Journal | J. Struct. Funct. Genomics |
PubMed ID | 19101823 |
PubMed Central ID | PMC2850604 |
Grant List | U54 GM074958-040005 / GM / NIGMS NIH HHS / United States U54-GM074958 / GM / NIGMS NIH HHS / United States |