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PDBsum entry 1g4y
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Signaling protein
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PDB id
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1g4y
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure of the gating domain of a ca2+-Activated k+ channel complexed with ca2+/calmodulin.
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Authors
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M.A.Schumacher,
A.F.Rivard,
H.P.Bächinger,
J.P.Adelman.
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Ref.
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Nature, 2001,
410,
1120-1124.
[DOI no: ]
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PubMed id
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Abstract
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Small-conductance Ca2+-activated K+ channels (SK channels) are independent of
voltage and gated solely by intracellular Ca2+. These membrane channels are
heteromeric complexes that comprise pore-forming alpha-subunits and the
Ca2+-binding protein calmodulin (CaM). CaM binds to the SK channel through the
CaM-binding domain (CaMBD), which is located in an intracellular region of the
alpha-subunit immediately carboxy-terminal to the pore. Channel opening is
triggered when Ca2+ binds the EF hands in the N-lobe of CaM. Here we report the
1.60 A crystal structure of the SK channel CaMBD/Ca2+/CaM complex. The CaMBD
forms an elongated dimer with a CaM molecule bound at each end; each CaM wraps
around three alpha-helices, two from one CaMBD subunit and one from the other.
As only the CaM N-lobe has bound Ca2+, the structure provides a view of both
calcium-dependent and -independent CaM/protein interactions. Together with
biochemical data, the structure suggests a possible gating mechanism for the SK
channel.
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Figure 2.
Figure 2: Interactions between CaMBD and CaM. a,
Ca^2+-dependent interactions between the CaMBD and the CaM
N-lobe. CaMBD subunits and CaM are coloured as in Fig. 1.
Hydrogen-bond interactions are indicated as black lines. The van
der Waals surface (yellow) is shown for the single 'leucine
prong'. b, Tethering contacts between CaMBD and CaM highlight
interactions between the CaM N-lobe and the second CaMBD dimer
(blue), where the contacts to the first subunit are shown in a.
c, Ca^2+-independent interactions between the CaMBD and the CaM
C-lobe. The van der Waals surface (cyan) is shown for the three
distinct prongs that interact with this lobe, Ala 425, Leu 428
and Trp 432.
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Figure 3.
Figure 3: Structure of CaM lobes in the CaMBD/Ca^2+/CaM complex.
a, Left, C  superimposition
of N-lobe residues 10 -67 of the CaMBD/Ca^2+/CaM complex (blue)
onto those of the Ca^2+/CaM complex12 (yellow). Ca^2+ ions are
shown as spheres. Right, C superimposition
of C-lobe residues 81 -146 of the CaMBD/Ca^2+/CaM complex (blue)
and the NMR apoCaM C-lobe structure^15 (magenta) onto that of
the Ca^2+/CaM complex12 (yellow). b, Comparison of the C-lobe EF
hand regions of the Ca^2+/CaM12 and the CaMBD/Ca^2+/CaM
complexes. Ca^2+-coordinating residues are shown as sticks. Note
the displacements of Ca^2+-coordinating residues Asp 95, Asp
131, Glu 104 and Glu 140 out of the expanded Ca^2+-coordination
sphere in the CaMBD complex.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2001,
410,
1120-1124)
copyright 2001.
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