spacer
spacer

PDBsum entry 2f3y
Go to PDB code: 
protein metals Protein-protein interface(s) links
Metal binding protein PDB id
2f3y

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
146 a.a. *
18 a.a. *
Metals
_MG ×2
_CA ×4
Waters ×331
* Residue conservation analysis
PDB id:
2f3y
Name: Metal binding protein
Title: Calmodulin/iq domain complex
Structure: Calmodulin. Chain: a. Synonym: cam. Engineered: yes. Voltage-dependent l-type calcium channel alpha-1c subunit. Chain: b. Synonym: voltage- gated calcium channel alpha subunit cav1.2, calcium channel, l type, alpha-1 polypeptide, isoform 1, cardiac muscle. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: calm1, calm2, calm3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: the iq domain of the cardiac cav1.2 channel
Biol. unit: Dimer (from PQS)
Resolution:
1.45Å     R-factor:   0.189     R-free:   0.219
Authors: J.L.Fallon,F.A.Quiocho
Key ref:
J.L.Fallon et al. (2005). Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Ca(v)1.2 calcium channel. Structure, 13, 1881-1886. PubMed id: 16338416 DOI: 10.1016/j.str.2005.09.021
Date:
22-Nov-05     Release date:   27-Dec-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens
Seq:
Struc: 		149 a.a.
146 a.a.
Protein chain
Pfam   ArchSchema ?
Q13936  (CAC1C_HUMAN) -  Voltage-dependent L-type calcium channel subunit alpha-1C from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		2221 a.a.
18 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1016/j.str.2005.09.021 Structure 13:1881-1886 (2005)
PubMed id: 16338416  
 
 
Structure of calmodulin bound to the hydrophobic IQ domain of the cardiac Ca(v)1.2 calcium channel.
J.L.Fallon, D.B.Halling, S.L.Hamilton, F.A.Quiocho.
 
  ABSTRACT  
 
Ca2+-dependent inactivation (CDI) and facilitation (CDF) of the Ca(v)1.2 Ca2+ channel require calmodulin binding to a putative IQ motif in the carboxy-terminal tail of the pore-forming subunit. We present the 1.45 A crystal structure of Ca2+-calmodulin bound to a 21 residue peptide corresponding to the IQ domain of Ca(v)1.2. This structure shows that parallel binding of calmodulin to the IQ domain is governed by hydrophobic interactions. Mutations of residues I1672 and Q1673 in the peptide to alanines, which abolish CDI but not CDF in the channel, do not greatly alter the structure. Both lobes of Ca2+-saturated CaM bind to the IQ peptide but isoleucine 1672, thought to form an intramolecular interaction that drives CDI, is buried. These findings suggest that this structure could represent the conformation that calmodulin assumes in CDF.
 
  Selected figure(s)  
 
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 reprinted by permission from Cell Press: Structure (2005, 13, 1881-1886) copyright 2005.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20953164 E.Y.Kim, C.H.Rumpf, F.Van Petegem, R.J.Arant, F.Findeisen, E.S.Cooley, E.Y.Isacoff, and D.L.Minor (2010).
Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization.
  EMBO J, 29, 3924-3938.
PDB code: 3oxq
21134641 F.Findeisen, and D.L.Minor (2010).
Structural basis for the differential effects of CaBP1 and calmodulin on Ca(V)1.2 calcium-dependent inactivation.
  Structure, 18, 1617-1631.
PDB codes: 3ox5 3ox6
  20194603 J.Cui (2010).
Reduction of CaV channel activities by Ca2+-CaM: inactivation or deactivation?
  J Gen Physiol, 135, 297-301.  
20201898 S.Movafagh, and M.Morad (2010).
L-type calcium channel as a cardiac oxygen sensor.
  Ann N Y Acad Sci, 1188, 153-158.  
19998355 Y.Zhang, H.Tan, G.Chen, and Z.Jia (2010).
Investigating the disorder-order transition of calmodulin binding domain upon binding calmodulin using molecular dynamics simulation.
  J Mol Recognit, 23, 360-368.  
19074138 B.Chagot, F.Potet, J.R.Balser, and W.J.Chazin (2009).
Solution NMR Structure of the C-terminal EF-hand Domain of Human Cardiac Sodium Channel NaV1.5.
  J Biol Chem, 284, 6436-6445.
PDB code: 2kbi
19473981 D.B.Halling, D.K.Georgiou, D.J.Black, G.Yang, J.L.Fallon, F.A.Quiocho, S.E.Pedersen, and S.L.Hamilton (2009).
Determinants in CaV1 channels that regulate the Ca2+ sensitivity of bound calmodulin.
  J Biol Chem, 284, 20041-20051.
PDB code: 2vay
  19237593 F.Findeisen, and D.L.Minor (2009).
Disruption of the IS6-AID linker affects voltage-gated calcium channel inactivation and facilitation.
  J Gen Physiol, 133, 327-343.  
19667066 H.Ishida, M.Rainaldi, and H.J.Vogel (2009).
Structural studies of soybean calmodulin isoform 4 bound to the calmodulin-binding domain of tobacco mitogen-activated protein kinase phosphatase-1 provide insights into a sequential target binding mode.
  J Biol Chem, 284, 28292-28305.
PDB code: 2kn2
19066990 J.J.Stewart (2009).
Application of the PM6 method to modeling proteins.
  J Mol Model, 15, 765-805.  
19279214 J.L.Fallon, M.R.Baker, L.Xiong, R.E.Loy, G.Yang, R.T.Dirksen, S.L.Hamilton, and F.A.Quiocho (2009).
Crystal structure of dimeric cardiac L-type calcium channel regulatory domains bridged by Ca2+* calmodulins.
  Proc Natl Acad Sci U S A, 106, 5135-5140.
PDB code: 3g43
19717559 K.Griessmeier, H.Cuny, K.Rötzer, O.Griesbeck, H.Harz, M.Biel, and C.Wahl-Schott (2009).
Calmodulin is a functional regulator of Cav1.4 L-type Ca2+ channels.
  J Biol Chem, 284, 29809-29816.  
19808664 M.F.Sarhan, F.Van Petegem, and C.A.Ahern (2009).
A double tyrosine motif in the cardiac sodium channel domain III-IV linker couples calcium-dependent calmodulin binding to inactivation gating.
  J Biol Chem, 284, 33265-33274.  
19106096 Q.K.Kleerekoper, and J.A.Putkey (2009).
PEP-19, an Intrinsically Disordered Regulator of Calmodulin Signaling.
  J Biol Chem, 284, 7455-7464.  
  19342611 S.Dai, D.D.Hall, and J.W.Hell (2009).
Supramolecular assemblies and localized regulation of voltage-gated ion channels.
  Physiol Rev, 89, 411-452.  
19583261 S.J.Abraham, R.P.Nolet, R.J.Calvert, L.M.Anderson, and V.Gaponenko (2009).
The hypervariable region of K-Ras4B is responsible for its specific interactions with calmodulin.
  Biochemistry, 48, 7575-7583.  
19089983 T.I.Evans, and M.A.Shea (2009).
Energetics of calmodulin domain interactions with the calmodulin binding domain of CaMKII.
  Proteins, 76, 47-61.  
19129176 V.Z.Miloushev, J.A.Levine, M.A.Arbing, J.F.Hunt, G.S.Pitt, and A.G.Palmer (2009).
Solution Structure of the NaV1.2 C-terminal EF-hand Domain.
  J Biol Chem, 284, 6446-6454.
PDB code: 2kav
19340532 W.Y.Wang, L.Y.Hao, E.Minobe, Z.A.Saud, D.Y.Han, and M.Kameyama (2009).
CaMKII phosphorylates a threonine residue in the C-terminal tail of Cav1.2 Ca(2+) channel and modulates the interaction of the channel with calmodulin.
  J Physiol Sci, 59, 283-290.  
18940602 E.Y.Kim, C.H.Rumpf, Y.Fujiwara, E.S.Cooley, F.Van Petegem, and D.L.Minor (2008).
Structures of CaV2 Ca2+/CaM-IQ domain complexes reveal binding modes that underlie calcium-dependent inactivation and facilitation.
  Structure, 16, 1455-1467.
PDB codes: 3dve 3dvj 3dvk 3dvm
18266933 I.Calin-Jageman, and A.Lee (2008).
Ca(v)1 L-type Ca2+ channel signaling complexes in neurons.
  J Neurochem, 105, 573-583.  
17991744 J.A.Putkey, M.N.Waxham, T.R.Gaertner, K.J.Brewer, M.Goldsmith, Y.Kubota, and Q.K.Kleerekoper (2008).
Acidic/IQ motif regulator of calmodulin.
  J Biol Chem, 283, 1401-1410.  
18718913 J.Ohrtman, B.Ritter, A.Polster, K.G.Beam, and S.Papadopoulos (2008).
Sequence differences in the IQ motifs of CaV1.1 and CaV1.2 strongly impact calmodulin binding and calcium-dependent inactivation.
  J Biol Chem, 283, 29301-29311.  
18400181 M.X.Mori, C.W.Vander Kooi, D.J.Leahy, and D.T.Yue (2008).
Crystal structure of the CaV2 IQ domain in complex with Ca2+/calmodulin: high-resolution mechanistic implications for channel regulation by Ca2+.
  Structure, 16, 607-620.  
18819009 S.J.Abraham, S.Hoheisel, and V.Gaponenko (2008).
Detection of protein-ligand interactions by NMR using reductive methylation of lysine residues.
  J Biomol NMR, 42, 143-148.  
17224447 A.L.Tippens, and A.Lee (2007).
Caldendrin, a neuron-specific modulator of Cav/1.2 (L-type) Ca2+ channels.
  J Biol Chem, 282, 8464-8473.  
  19704657 A.P.Yamniuk, M.Rainaldi, and H.J.Vogel (2007).
Calmodulin has the Potential to Function as a Ca-Dependent Adaptor Protein.
  Plant Signal Behav, 2, 354-357.  
17521566 D.L.Minor (2007).
The neurobiologist's guide to structural biology: a primer on why macromolecular structure matters and how to evaluate structural data.
  Neuron, 54, 511-533.  
  17438121 K.Dunlap (2007).
Calcium channels are models of self-control.
  J Gen Physiol, 129, 379-383.  
16844751 A.Ganoth, R.Friedman, E.Nachliel, and M.Gutman (2006).
A molecular dynamics study and free energy analysis of complexes between the Mlc1p protein and two IQ motif peptides.
  Biophys J, 91, 2436-2450.  
16921373 A.Singh, D.Hamedinger, J.C.Hoda, M.Gebhart, A.Koschak, C.Romanin, and J.Striessnig (2006).
C-terminal modulator controls Ca2+-dependent gating of Ca(v)1.4 L-type Ca2+ channels.
  Nat Neurosci, 9, 1108-1116.  
17052221 F.Van Petegem, and D.L.Minor (2006).
The structural biology of voltage-gated calcium channel function and regulation.
  Biochem Soc Trans, 34, 887-893.  
16956364 J.Martinez-Sanz, A.Yang, Y.Blouquit, P.Duchambon, L.Assairi, and C.T.Craescu (2006).
Binding of human centrin 2 to the centrosomal protein hSfi1.
  FEBS J, 273, 4504-4515.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

spacer
spacer