The
NMR structure of a UBA domain from the protein
ubiquilin-1 (top, cyan) bound to
ubiquitin (bottom, orange), illustrating the
three-helix bundle structure of the UBA domain. Isoleucine 44, the center of a hydrophobic patch on the ubiquitin surface that interacts with a number of
ubiquitin-binding domains, is highlighted in blue. Rendered from PDB:
2JY6.[1]
Protein degradation via the ubiquitin proteasome system (UPS) allows the cell to selectively negatively regulate intracellular proteins. Protein degradation helps to maintain protein quality control, signalling, and cell cycle progression.[5][6]
UBA has been proposed to limit ubiquitin chain elongation and to target polyubiquitinated proteins to
the 26S
proteasome for degradation.[7] They have been identified in modular
proteins involved in protein trafficking,
DNA repair,
proteasomal degradation, and cell cycle regulation.
The
humanhomologue of
yeast Rad23A is one example of a
nucleotide excision-repair protein that contains both an internal and a C-terminal UBA
domain. The solution
structure of
human Rad23A UBA(2) showed that the domain forms a compact three-helix bundle.[10]
Comparison of the
structures of UBA(1) and UBA(2) reveals that both form very similar
folds and have a
conserved large
hydrophobic surface patch which may be a common protein-interacting surface present in diverse UBA
domains. Evidence that
ubiquitinbinds to UBA domains leads to the prediction that the
hydrophobic surface patch of UBA domains
interacts with the
hydrophobic surface on the five-stranded
beta-sheet of ubiquitin.[11]
^Hofmann K, Bucher P (May 1996). "The UBA domain: a sequence motif present in multiple enzyme classes of the ubiquitination pathway". Trends in Biochemical Sciences. 21 (5): 172–3.
doi:
10.1016/S0968-0004(96)30015-7.
PMID8871400.
^
abKawashima, Takemasa; Berthet-Colominas, Carmen; Wulff, Michael; Cusack, Stephen; Leberman, Reuben (8 February 1996). "The structure of the Escherichia coli EF-Tu· EF-Ts complex at 2.5 Å resolution". Nature. 379 (6565): 511–518.
Bibcode:
1996Natur.379..511K.
doi:
10.1038/379511a0.
PMID8596629.
S2CID4273375.
^Dieckmann T, Withers-Ward ES, Jarosinski MA, Liu CF, Chen IS, Feigon J (December 1998). "Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr". Nature Structural Biology. 5 (12): 1042–7.
doi:
10.1038/4220.
PMID9846873.
S2CID30478711.
^Mueller TD, Feigon J (June 2002). "Solution structures of UBA domains reveal a conserved hydrophobic surface for protein-protein interactions". Journal of Molecular Biology. 319 (5): 1243–55.
doi:
10.1016/S0022-2836(02)00302-9.
PMID12079361.
This article incorporates text from the public domain
Pfam and
InterPro: