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PDBsum entry 3drx
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Unknown function
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PDB id
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3drx
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References listed in PDB file
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Key reference
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Title
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Pentameric assembly of potassium channel tetramerization domain-Containing protein 5.
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Authors
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I.S.Dementieva,
V.Tereshko,
Z.A.Mccrossan,
E.Solomaha,
D.Araki,
C.Xu,
N.Grigorieff,
S.A.Goldstein.
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Ref.
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J Mol Biol, 2009,
387,
175-191.
[DOI no: ]
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PubMed id
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Abstract
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We report the X-ray crystal structure of human potassium channel tetramerization
domain-containing protein 5 (KCTD5), the first member of the family to be so
characterized. Four findings were unexpected. First, the structure reveals
assemblies of five subunits while tetramers were anticipated; pentameric
stoichiometry is observed also in solution by scanning transmission electron
microscopy mass analysis and analytical ultracentrifugation. Second, the same
BTB (bric-a-brac, tramtrack, broad complex) domain surface mediates the assembly
of five KCTD5 and four voltage-gated K(+) (Kv) channel subunits; four amino acid
differences appear crucial. Third, KCTD5 complexes have well-defined N- and
C-terminal modules separated by a flexible linker that swivels by approximately
30 degrees; the C-module shows a new fold and is required to bind Golgi
reassembly stacking protein 55 with approximately 1 microM affinity, as judged
by surface plasmon resonance and ultracentrifugation. Fourth, despite the
homology reflected in its name, KCTD5 does not impact the operation of Kv4.2,
Kv3.4, Kv2.1, or Kv1.2 channels.
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Figure 2.
Fig. 2. Structural determinants of the KCTD5 central cavity.
A KCTD5 subunit in ribbon presentation showing the four segments
(L1–L4) of the BTB fold and the central cavity of the pentamer
assembly in cut-away. The residues that shape the central cavity
are labeled in ball-and-stick mode; also shown are the
solvent-accessible surfaces and cavity dimensions.
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Figure 5.
Fig. 5. Intermolecular interfaces in KCTD5 assemblies. (a)
Potential surfaces of individual KCTD subunit N- and C-modules.
Indicated in red are acidic Asp83, Asp93, Asp95, Asp116, Glu124,
Glu165–Glu167, Glu196, Asp197, Glu182, and Glu208; basic
residues Arg107, Lys110, and Lys115 are indicated in blue.
Gly51, Leu56, Thr57, Thr61, Leu91, Gly100, Asn114, and Gln183
are noted in gray. (b) Secondary structural elements at the
interface of adjacent subunits in the N-module viewed from the
center of the assembly. α-Helices and β-strands are depicted
as cylinders and arrows, respectively. The L1–L4 segments of
the BTB fold are shown in colors as per Fig. 2. Inset presents
an expanded view of the boxed area. Residues that form
interfaces are shown in ball-and-stick in yellow (subunit 1) and
gray (subunit 2). H-bonds (2.6–3.4 Å) are indicated with
dotted lines. Asp116 (subunit 1) and Lys115 (subunit 2) interact
via main-chain atoms, and their side chains are omitted for
clarity. H-bond pairs and distances are noted in further detail
in Fig. S2a. (c) Secondary structural elements at the interface
of adjacent subunits in the C-module viewed from the center of
the assembly as in (b). Inset presents an expanded view of the
boxed area as in (b). H-bond pairs and distances are noted in
further detail in Fig. S2b.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2009,
387,
175-191)
copyright 2009.
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