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PDBsum entry 2oxq
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References listed in PDB file
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Key reference
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Title
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Interactions between the quality control ubiquitin ligase chip and ubiquitin conjugating enzymes.
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Authors
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Z.Xu,
E.Kohli,
K.I.Devlin,
M.Bold,
J.C.Nix,
S.Misra.
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Ref.
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Bmc Struct Biol, 2008,
8,
26-26.
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PubMed id
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Abstract
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BACKGROUND: Ubiquitin (E3) ligases interact with specific ubiquitin conjugating
(E2) enzymes to ubiquitinate particular substrate proteins. As the combination
of E2 and E3 dictates the type and biological consequence of ubiquitination, it
is important to understand the basis of specificity in E2:E3 interactions. The
E3 ligase CHIP interacts with Hsp70 and Hsp90 and ubiquitinates client proteins
that are chaperoned by these heat shock proteins. CHIP interacts with two types
of E2 enzymes, UbcH5 and Ubc13-Uev1a. It is unclear, however, why CHIP binds
these E2 enzymes rather than others, and whether CHIP interacts preferentially
with UbcH5 or Ubc13-Uev1a, which form different types of polyubiquitin chains.
RESULTS: The 2.9 A crystal structure of the CHIP U-box domain complexed with
UbcH5a shows that CHIP binds to UbcH5 and Ubc13 through similar specificity
determinants, including a key S-P-A motif on the E2 enzymes. The determinants
make different relative contributions to the overall interactions between CHIP
and the two E2 enzymes. CHIP undergoes auto-ubiquitination by UbcH5 but not by
Ubc13-Uev1a. Instead, CHIP drives the formation of unanchored polyubiquitin by
Ubc13-Uev1a. CHIP also interacts productively with the class III E2 enzyme
Ube2e2, in which the UbcH5- and Ubc13-binding specificity determinants are
highly conserved. CONCLUSION: The CHIP:UbcH5a structure emphasizes the
importance of specificity determinants located on the long loops and central
helix of the CHIP U-box, and on the N-terminal helix and loops L4 and L7 of its
cognate E2 enzymes. The S-P-A motif and other specificity determinants define
the set of cognate E2 enzymes for CHIP, which likely includes several Class III
E2 enzymes. CHIP's interactions with UbcH5, Ube2e2 and Ubc13-Uev1a are
consistent with the notion that Ubc13-Uev1a may work sequentially with other E2
enzymes to carry out K63-linked polyubiquitination of CHIP substrates.
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