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PDBsum entry 3b0f
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Protein binding
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PDB id
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3b0f
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the ubiquitin-Associated (uba) domain of p62 and its interaction with ubiquitin.
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Authors
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S.Isogai,
D.Morimoto,
K.Arita,
S.Unzai,
T.Tenno,
J.Hasegawa,
Y.S.Sou,
M.Komatsu,
K.Tanaka,
M.Shirakawa,
H.Tochio.
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Ref.
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J Biol Chem, 2011,
286,
31864-31874.
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
92%.
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Abstract
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p62/SQSTM1/A170 is a multimodular protein that is found in ubiquitin-positive
inclusions associated with neurodegenerative diseases. Recent findings indicate
that p62 mediates the interaction between ubiquitinated proteins and
autophagosomes, leading these proteins to be degraded via the
autophagy-lysosomal pathway. This ubiquitin-mediated selective autophagy is
thought to begin with recognition of the ubiquitinated proteins by the
C-terminal ubiquitin-associated (UBA) domain of p62. We present here the crystal
structure of the UBA domain of mouse p62 and the solution structure of its
ubiquitin-bound form. The p62 UBA domain adopts a novel dimeric structure in
crystals, which is distinctive from those of other UBA domains. NMR analyses
reveal that in solution the domain exists in equilibrium between the dimer and
monomer forms, and binding ubiquitin shifts the equilibrium toward the monomer
to form a 1:1 complex between the UBA domain and ubiquitin. The dimer-to-monomer
transition is associated with a structural change of the very C-terminal end of
the p62 UBA domain, although the UBA fold itself is essentially maintained. Our
data illustrate that dimerization and ubiquitin binding of the p62 UBA domain
are incompatible with each other. These observations reveal an autoinhibitory
mechanism in the p62 UBA domain and suggest that autoinhibition plays a role in
the function of p62.
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