PDBsum entry 3dvj

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protein metals Protein-protein interface(s) links
Membrane protein PDB id
Protein chains
140 a.a. *
21 a.a. *
_CA ×4
Waters ×10
* Residue conservation analysis
PDB id:
Name: Membrane protein
Title: Crystal structure of ca2+/cam-cav2.2 iq domain (without clon artifact, hm to tv) complex
Structure: Calmodulin. Chain: a. Synonym: cam. Engineered: yes. Voltage-dependent n-type calcium channel subunit chain: b. Fragment: unp residues 1853-1873. Synonym: voltage-gated calcium channel subunit alpha cav2.2 channel, l type, alpha-1 polypeptide isoform 5, brain calci
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: calm1, calm, cam, cam1, calm2, cam2, camb, calm3, cal cam3, camc, camiii. Expressed in: escherichia coli. Expression_system_taxid: 562. Oryctolagus cuniculus. Rabbit.
2.80Å     R-factor:   0.250     R-free:   0.298
Authors: E.Y.Kim,C.H.Rumpf,Y.Fujiwara,E.S.Cooley,F.Van Petegem,D.L.Mi
Key ref:
E.Y.Kim et al. (2008). Structures of CaV2 Ca2+/CaM-IQ domain complexes reveal binding modes that underlie calcium-dependent inactivation and facilitation. Structure, 16, 1455-1467. PubMed id: 18940602 DOI: 10.1016/j.str.2008.07.010
18-Jul-08     Release date:   04-Nov-08    
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Protein chain
Pfam   ArchSchema ?
P62158  (CALM_HUMAN) -  Calmodulin
149 a.a.
140 a.a.
Protein chain
Pfam   ArchSchema ?
Q05152  (CAC1B_RABIT) -  Voltage-dependent N-type calcium channel subunit alpha-1B
2339 a.a.
21 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   17 terms 
  Biological process     Fc-epsilon receptor signaling pathway   50 terms 
  Biochemical function     enzyme regulator activity     20 terms  


DOI no: 10.1016/j.str.2008.07.010 Structure 16:1455-1467 (2008)
PubMed id: 18940602  
Structures of CaV2 Ca2+/CaM-IQ domain complexes reveal binding modes that underlie calcium-dependent inactivation and facilitation.
E.Y.Kim, C.H.Rumpf, Y.Fujiwara, E.S.Cooley, F.Van Petegem, D.L.Minor.
Calcium influx drives two opposing voltage-activated calcium channel (Ca(V)) self-modulatory processes: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Specific Ca(2+)/calmodulin (Ca(2+)/CaM) lobes produce CDI and CDF through interactions with the Ca(V)alpha(1) subunit IQ domain. Curiously, Ca(2+)/CaM lobe modulation polarity appears inverted between Ca(V)1s and Ca(V)2s. Here, we present crystal structures of Ca(V)2.1, Ca(V)2.2, and Ca(V)2.3 Ca(2+)/CaM-IQ domain complexes. All display binding orientations opposite to Ca(V)1.2 with a physical reversal of the CaM lobe positions relative to the IQ alpha-helix. Titration calorimetry reveals lobe competition for a high-affinity site common to Ca(V)1 and Ca(V)2 IQ domains that is occupied by the CDI lobe in the structures. Electrophysiological experiments demonstrate that the N-terminal Ca(V)2 Ca(2+)/C-lobe anchors affect CDF. Together, the data unveil the remarkable structural plasticity at the heart of Ca(V) feedback modulation and indicate that Ca(V)1 and Ca(V)2 IQ domains bear a dedicated CDF site that exchanges Ca(2+)/CaM lobe occupants.
  Selected figure(s)  
Figure 2.
Figure 2. Ca^2+/CaM-Ca[V]2 Interaction Details
(A) Ca[V]2.3 Ca^2+/N-lobe.
(B) Ca[V]2.2 Ca^2+/N-lobe.
(C) Ca[V]2.3 Ca^2+/C-lobe.
(D) Ca[V]2.2 Ca^2+/C-lobe.The IQ domain as shown in stick representation with major anchor positions colored white. As Ca[V]2.1 and Ca[V]2.3 structures are equivalent and the Ca[V]2.3 structure is higher resolution, we only show Ca[V]2.3 here. Ca^2+/CaM lobes are shown in surface representation. Residues contributing to hydrophobic (yellow), negatively charged (red), positively charged (blue), and polar (green) interactions (≤4 Å) to the IQ domain indicated. Labels for IQ domain residues are boxed.
(E) Diagram of the major Ca[V]1 and Ca[V]2 IQ domain anchor positions. The isoleucine of the IQ motif is labeled as position 0. Ca[V]2.1, Ca[V]2.2, and Ca[V]2.3 major anchors are shown by yellow, purple, and orange ovals, respectively. Ca[V]1.2 anchor positions are shown by red squares.
Figure 3.
Figure 3. ITC Characterization of Ca^2+/CaM-Ca[V]2.1 IQ Domain Interactions
(A) 75 μM Ca^2+/N-lobe into 7.5 μM Ca[V]2.1 IQ domain.
(B) 75 μM Ca^2+/C-lobe into 7.5 μM Ca[V]2.1 IQ domain.
(C) 75 μM Ca^2+/N-lobe into 7.5 μM Ca[V]2.1 IQ domain Y1974A (position (+3)).
(D) 75 μM Ca^2+/C-lobe into 7.5 μM Ca[V]2.1 IQ domain Y1974A (position (+3)).
(E) 250 μM Ca^2+/C-lobe into a solution of 25 μM Ca[V]2.1 IQ domain and 33 μM Ca^2+/N-lobe.
(F) 250 μM Ca^2+/C-lobe into a solution of 25 μM Ca[V]2.1 IQ domain I1965A (position (−6)), and 33 μM Ca^2+/N-lobe.
(G) 250 μM Ca^2+/C-lobe into a solution of 25 μM Ca[V]2.1 IQ domain M1969A (position (−2)), and 33 μM Ca^2+/N-lobe.
(H) Comparison Ca^2+/C-lobe binding isotherms to Ca^2+/N-lobe-Ca[V]2.1 IQ domain complexes. ITC Panels show addition of 10 μl aliquots of titrant to the target (top) and binding isotherms (bottom). Cartoons depict the observed binding modes. Stars indicate mutant peptides and site of mutation.
  The above figures are reprinted from an Open Access publication published by Cell Press: Structure (2008, 16, 1455-1467) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20686800 B.Holakovska, L.Grycova, J.Bily, and J.Teisinger (2011).
Characterization of calmodulin binding domains in TRPV2 and TRPV5 C-tails.
  Amino Acids, 40, 741-748.  
  21139419 D.L.Minor, and F.Findeisen (2010).
Progress in the structural understanding of voltage-gated calcium channel (CaV) function and modulation.
  Channels (Austin), 4, 459-474.  
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
  19906882 L.Kreiner, C.J.Christel, M.Benveniste, B.Schwaller, and A.Lee (2010).
Compensatory regulation of Cav2.1 Ca2+ channels in cerebellar Purkinje neurons lacking parvalbumin and calbindin D-28k.
  J Neurophysiol, 103, 371-381.  
20213668 R.J.Falconer, A.Penkova, I.Jelesarov, and B.M.Collins (2010).
Survey of the year 2008: applications of isothermal titration calorimetry.
  J Mol Recognit, 23, 395-413.  
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
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.  
19675352 X.Xu, and H.M.Colecraft (2009).
Engineering proteins for custom inhibition of Ca(V) channels.
  Physiology (Bethesda), 24, 210-218.  
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.