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PDBsum entry 4uij
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Signaling protein
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PDB id
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4uij
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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 complexity in the kctd family of cullin3-Dependent e3 ubiquitin ligases.
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Authors
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D.M.Pinkas,
C.E.Sanvitale,
J.C.Bufton,
F.J.Sorrell,
N.Solcan,
R.Chalk,
J.Doutch,
A.N.Bullock.
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Ref.
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Biochem J, 2017,
474,
3747-3761.
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PubMed id
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Abstract
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Members of the potassium channel tetramerization domain (KCTD) family are
soluble non-channel proteins that commonly function as Cullin3 (Cul3)-dependent
E3 ligases. Solution studies of the N-terminal BTB domain have suggested that
some KCTD family members may tetramerize similarly to the homologous
tetramerization domain (T1) of the voltage-gated potassium (Kv) channels.
However, available structures of KCTD1, KCTD5 and KCTD9 have demonstrated
instead pentameric assemblies. To explore other phylogenetic clades within the
KCTD family, we determined the crystal structures of the BTB domains of a
further five human KCTD proteins revealing a rich variety of oligomerization
architectures, including monomer (SHKBP1), a novel two-fold symmetric tetramer
(KCTD10 and KCTD13), open pentamer (KCTD16) and closed pentamer (KCTD17). While
these diverse geometries were confirmed by small-angle X-ray scattering (SAXS),
only the pentameric forms were stable upon size-exclusion chromatography. With
the exception of KCTD16, all proteins bound to Cul3 and were observed to
reassemble in solution as 5 : 5 heterodecamers. SAXS data and structural
modelling indicate that Cul3 may stabilize closed BTB pentamers by binding
across their BTB-BTB interfaces. These extra interactions likely also allow KCTD
proteins to bind Cul3 without the expected 3-box motif. Overall, these studies
reveal the KCTD family BTB domain to be a highly versatile scaffold compatible
with a range of oligomeric assemblies and geometries. This observed interface
plasticity may support functional changes in regulation of this unusual E3
ligase family.
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