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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

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. a-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:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
980365
Report Number(s):
BNL-93283-2010-JA
TRN: US201015%%1750
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
Journal of Structural and Functional Genomics
Additional Journal Information:
Journal Volume: 10
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; CRYSTALLOGRAPHY; CRYSTALS; ENZYMES; FUNCTIONALS; FUNCTIONS; HUMAN POPULATIONS; NUCLEAR MAGNETIC RESONANCE; PROTEINS; RESOLUTION; SOLVENTS; SPECIFICITY; SPECTROSCOPY; TARGETS; WELLS; national synchrotron light source

Citation Formats

Liu, G, Forouhar, F, Eletsky, A, Atreya, H, Aramini, J, Xiao, R, Montelione, G, Hunt, J, Szyperski, T, and et. al. 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. United States: N. p., 2009. Web. doi:10.1007/s10969-008-9054-7.
Liu, G, Forouhar, F, Eletsky, A, Atreya, H, Aramini, J, Xiao, R, Montelione, G, Hunt, J, Szyperski, T, & et. al. 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. United States. doi:10.1007/s10969-008-9054-7.
Liu, G, Forouhar, F, Eletsky, A, Atreya, H, Aramini, J, Xiao, R, Montelione, G, Hunt, J, Szyperski, T, and et. al. Thu . "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". United States. doi:10.1007/s10969-008-9054-7.
@article{osti_980365,
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},
author = {Liu, G and Forouhar, F and Eletsky, A and Atreya, H and Aramini, J and Xiao, R and Montelione, G and Hunt, J and Szyperski, T and et. al.},
abstractNote = {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. a-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},
journal = {Journal of Structural and Functional Genomics},
number = ,
volume = 10,
place = {United States},
year = {2009},
month = {1}
}