 |
PDBsum entry 3g43
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Metal binding protein
|
PDB id
|
|
|
|
3g43
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
75 a.a.
|
|
|
|
|
|
|
|
|
|
|
147 a.a.
|
|
|
|
|
|
|
|
|
|
|
68 a.a.
|
|
|
|
|
|
|
|
|
|
|
45 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Crystal structure of dimeric cardiac l-Type calcium channel regulatory domains bridged by ca2+ Calmodulins.
|
|
|
Authors
|
|
J.L.Fallon,
M.R.Baker,
L.Xiong,
R.E.Loy,
G.Yang,
R.T.Dirksen,
S.L.Hamilton,
F.A.Quiocho.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2009,
106,
5135-5140.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
|
|
|
|
Abstract
|
|
|
Voltage-dependent calcium channels (Ca(V)) open in response to changes in
membrane potential, but their activity is modulated by Ca(2+) binding to
calmodulin (CaM). Structural studies of this family of channels have focused on
CaM bound to the IQ motif; however, the minimal differences between structures
cannot adequately describe CaM's role in the regulation of these channels. We
report a unique crystal structure of a 77-residue fragment of the Ca(V)1.2
alpha(1) subunit carboxyl terminus, which includes a tandem of the pre-IQ and IQ
domains, in complex with Ca(2+).CaM in 2 distinct binding modes. The structure
of the Ca(V)1.2 fragment is an unusual dimer of 2 coiled-coiled pre-IQ regions
bridged by 2 Ca(2+).CaMs interacting with the pre-IQ regions and a canonical
Ca(V)1-IQ-Ca(2+).CaM complex. Native Ca(V)1.2 channels are shown to be a mixture
of monomers/dimers and a point mutation in the pre-IQ region predicted to
abolish the coiled-coil structure significantly reduces Ca(2+)-dependent
inactivation of heterologously expressed Ca(V)1.2 channels.
|
|
|
|
|
|
|
|
Figure 1.
Crystal structure of the C-terminal pre-IQ-IQ fragment from
the Ca[V]1.2 α[1] subunit. CaM N-lobes/domains are tan; C-lobes
light blue; Ca^2+ ions are gold spheres. Ca[V]1.2 fragments (I
and II) are blue to orange rainbow starting from the N termini
(marked with N); the IQ domain for fragment I is red. Loop
regions, the IQ domain for fragment II, and the C-domain of CaM
IV are not seen in the density and are modeled, by analogy with
fragment I and CaM III, as thin light gray lines for reference.
The N- and C-lobes of the extended form of CaMs I and II
bridging the pre-IQ segments are separated by ≈15 Å,
whereas those of CaM III bound to the IQ motif of Ca[V]I
fragment make contacts. Figs. 1 and 2 were made with PyMOL
(www.pymol.org).
|
|
Figure 3.
Schematic diagram of the residue contacts (<4.5 Å
distance) of the Ca[v] I N-terminal region (T1609–1623; left
column) with primarily the N-lobe of CaM I (residues in tan) and
Ca[v] II C-terminal region (1633–1649; right column) with
mainly the C-lobe of CaM I (residues in light blue). The total
contacts of nonhydrogen atoms between Ca[v] I N-terminal region
and CaM I N-lobe/C-lobe is ≈200 and that between Ca[v] II
C-terminal region and CaM I C-lobe/N-lobe is ≈260. Similar
contacts are made with CaM II lobes.
|
|
|
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Structure of calmodulin bound to the hydrophobic iq domain of the cardiac ca(V)1.2 calcium channel.
|
|
|
Authors
|
|
J.L.Fallon,
D.B.Halling,
S.L.Hamilton,
F.A.Quiocho.
|
|
|
Ref.
|
|
Structure, 2005,
13,
1881-1886.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
Figure 2.
Figure 2. Views of Key Residues of the Bound IQ Peptide
with CaM Surfaces
The residues of the peptide are in
magenta, electron density is blue. Protein surface
representations are: dark blue, +; red, -; cyan, neutral or
nonpolar; and yellow, sulfur of methionine residues.
(A)
Cutaway view of the complex. CaM domains are labeled, along with
selected peptide residues. The N-terminal pocket of Ca^2+-CaM
(containing F1666 of the peptide) is to the left of center. Some
residues at the C-terminal end of the peptide extend above the
plane of the figure and are not shown.
(B) The N-terminal
hydrophobic cluster of the IQ peptide. F1666 (center background)
occupies the N-terminal hydrophobic pocket of Ca^2+CaM. The
surface is the CaM binding channel, with the N domain of
Ca^2+-CaM to the left and the C domain to the right. F1670,
Y1667, and L1671 are grouped near a nonpolar surface created by
the Ca^2+-CaM linker (lower foreground). This hydrophobic
surface is created by M71, M72, M76, and the hydrophobic portion
of the K75-E84 salt link.
(C) The C-terminal hydrophobic
cluster of the IQ peptide. The surface is the C-terminal
hydrophobic pocket of Ca^2+-CaM.
|
|
|
|
|
|
The above figure is
reproduced from the cited reference
with permission from Cell Press
|
|
|
|
|
|
|
