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PDBsum entry 3a1q
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Gene regulation/signaling protein
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PDB id
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3a1q
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References listed in PDB file
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Key reference
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Title
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Structural basis for specific recognition of lys 63-Linked polyubiquitin chains by tandem uims of rap80.
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Authors
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Y.Sato,
A.Yoshikawa,
H.Mimura,
M.Yamashita,
A.Yamagata,
S.Fukai.
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Ref.
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Embo J, 2009,
28,
2461-2468.
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PubMed id
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Abstract
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RAP80 has a key role in the recruitment of the Abraxas-BRCC36-BRCA1-BARD1
complex to DNA-damage foci for DNA repair through specific recognition of Lys
63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs
(UIMs). Here, we report the crystal structure of the RAP80 tandem UIMs
(RAP80-UIM1-UIM2) in complex with Lys 63-linked di-ubiquitin at 2.2 A
resolution. The two UIMs, UIM1 and UIM2, and the alpha-helical inter-UIM region
together form a continuous 60 A-long alpha-helix. UIM1 and UIM2 bind to the
proximal and distal ubiquitin moieties, respectively. Both UIM1 and UIM2 of
RAP80 recognize an Ile 44-centered hydrophobic patch on ubiquitin but neither
UIM interacts with the Lys 63-linked isopeptide bond. Our structure suggests
that the inter-UIM region forms a 12 A-long alpha-helix that ensures that the
UIMs are arranged to enable specific binding of Lys 63-linked di-ubiquitin. This
was confirmed by pull-down analyses using RAP80-UIM1-UIM2 mutants of various
length inter-UIM regions. Further, we show that the Epsin1 tandem UIM, which has
an inter-UIM region similar to that of RAP80-UIM1-UIM2, also selectively binds
Lys 63-linked di-ubiquitin.
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