PDBsum entry: 1t0h

Signaling protein

PDB-id

1t0h


	Biological unit* = asymmetric unit, as shown (as deduced by PQS*)

Contents

Description

Header details

Protein chains

Metal ions

_CL

Waters ×148

* Residue conservation analysis

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PDB id:

1t0h

Name:

Signaling protein

Title:

Crystal structure of the rattus norvegicus voltage gated calcium channel beta subunit isoform 2a

Structure:

Voltage-gated calcium channel subunit beta2a. Chain: a. Fragment: residues 17-145. Engineered: yes. Voltage-gated calcium channel subunit beta2a. Chain: b. Fragment: residues 203-425. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: cacnb2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biological unit:

Dimer (from PQS)

UniProt:

Chain A: Q8VGC3 (CACB2_RAT)

Seq:

Struc:


Seq:

Struc:


Seq:				655 a.a.

Struc:				96 a.a.

Chain B: Q8VGC3 (CACB2_RAT)

Seq:

Struc:

Seq:

Struc:

Seq:

655 a.a.

Struc:

187 a.a.*

Key:		PfamA domain
		Secondary structure			CATH domain

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Resolution:

1.97Å

R-factor:

0.187

R-free:

0.213

Authors:

F.Van Petegem,K.Clark,F.Chatelain,D.Minor Jr.

Key ref:

F.Van Petegem et al. (2004). Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.. Nature, 429, 671-675. [PubMed id: 15141227] [DOI: 10.1038/nature02588]

Date:

08-Apr-04

Release date:

15-Jun-04

Related entries:

1t0j

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Key reference

DOI no: 10.1038/nature02588 Nature 429:671-675 (2004)

PubMed id: 15141227

Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.

F.Van Petegem, K.A.Clark, F.C.Chatelain, D.L.Minor.

ABSTRACT

Voltage-gated calcium channels (Ca(V)s) govern muscle contraction, hormone and neurotransmitter release, neuronal migration, activation of calcium-dependent signalling cascades, and synaptic input integration. An essential Ca(V) intracellular protein, the beta-subunit (Ca(V)beta), binds a conserved domain (the alpha-interaction domain, AID) between transmembrane domains I and II of the pore-forming alpha(1) subunit and profoundly affects multiple channel properties such as voltage-dependent activation, inactivation rates, G-protein modulation, drug sensitivity and cell surface expression. Here, we report the high-resolution crystal structures of the Ca(V)beta2a conserved core, alone and in complex with the AID. Previous work suggested that a conserved region, the beta-interaction domain (BID), formed the AID-binding site; however, this region is largely buried in the Ca(V)beta core and is unavailable for protein-protein interactions. The structure of the AID-Ca(V)beta2a complex shows instead that Ca(V)beta2a engages the AID through an extensive, conserved hydrophobic cleft (named the alpha-binding pocket, ABP). The ABP-AID interaction positions one end of the Ca(V)beta near the intracellular end of a pore-lining segment, called IS6, that has a critical role in Ca(V) inactivation. Together, these data suggest that Ca(V)betas influence Ca(V) gating by direct modulation of IS6 movement within the channel pore.

Selected figure(s)

Figure 2.
Figure 2: Structural comparisons between PSD-95 (gold) and Ca[V] beta-[2a] (blue). a, Superposition of Ca[V] [2a] and PSD-95 nucleotide kinase domains (RMSD[C ]= 3.9 �). The dashed circle indicates the guanosine-monophosphate (GMP)-binding domain present in PSD-95 but absent in Ca[V] [2a]. The guanosine monophosphate molecule bound to PSD-95 is displayed in space-filling representation. Nucleotide kinase (NK) and SH3 domains are indicated. The relative change in SH3 domain orientation is indicated. b, Superposition of PSD-95 and Ca[V] [2a] SH3 domains (RMSD[C ]= 1.6 �). Position of the polyproline ligand from a superposition with the Sem5 SH3 domain (Protein Data Bank code 2SEM) (RMSD[C ]= 1.8 �) is shown in space-filling representation. The Sem5 SH3 is not shown. The DALI server generated the superpositions (http://www.ebi.ac.uk/dali/). Figure 4.
Figure 4: AID -ABP interactions. a, Surface representation of the Ca[V] [2a] ABP, bound to the AID. The AID (gold) is shown in stick representation. Y437 and W440 are white. Ca[V] [2a] residues that contribute hydrophobic (blue) and hydrogen bond (red) side-chain contacts to the AID are labelled. Select residues of the AID are labelled to orient the reader. b, c, Slices through the AID -ABP interaction at AID positions Y437 and W440 (gold). Labels indicate the AID residues.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2004, 429, 671-675) copyright 2004.

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id Reference

19840220 S.A.Abiria, and R.J.Colbran (2010).
CaMKII associates with CaV1.2 L-type calcium channels via selected beta subunits to enhance regulatory phosphorylation.

J Neurochem, 112, 150-161.

18651169 A.V.Dresviannikov, K.M.Page, J.Leroy, W.S.Pratt, and A.C.Dolphin (2009).
Determinants of the voltage dependence of G protein modulation within calcium channel beta subunits.

Pflugers Arch, 457, 743-756.

19492014 E.Kobrinsky, P.Abrahimi, S.Q.Duong, S.Thomas, J.B.Harry, C.Patel, Q.Z.Lao, and N.M.Soldatov (2009).
Effect of Ca(v)beta subunits on structural organization of Ca(v)1.2 calcium channels.

PLoS One, 4, e5587.

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.

19858356 J.Striessnig (2009).
An oily competition: role of beta subunit palmitoylation for Ca2+ channel modulation by fatty acids.

J Gen Physiol, 134, 363-367.

19606473 P.L.Hedley, P.Jørgensen, S.Schlamowitz, J.Moolman-Smook, J.K.Kanters, V.A.Corfield, and M.Christiansen (2009).
The genetic basis of Brugada syndrome: a mutation update.

Hum Mutat, 30, 1256-1266.

19862833 P.L.Hedley, P.Jørgensen, S.Schlamowitz, R.Wangari, J.Moolman-Smook, P.A.Brink, J.K.Kanters, V.A.Corfield, and M.Christiansen (2009).
The genetic basis of long QT and short QT syndromes: a mutation update.

Hum Mutat, 30, 1486-1511.

19693805 Q.Xu, and D.L.Minor (2009).
Crystal structure of a trimeric form of the K(V)7.1 (KCNQ1) A-domain tail coiled-coil reveals structural plasticity and context dependent changes in a putative coiled-coil trimerization motif.

Protein Sci, 18, 2100-2114.

PDB codes: 3hfc 3hfe

19858358 T.Mitra-Ganguli, I.Vitko, E.Perez-Reyes, and A.R.Rittenhouse (2009).
Orientation of palmitoylated CaVbeta2a relative to CaV2.2 is critical for slow pathway modulation of N-type Ca2+ current by tachykinin receptor activation.

J Gen Physiol, 134, 385-396.

19153575 W.Feng, and M.Zhang (2009).
Organization and dynamics of PDZ-domain-related supramodules in the postsynaptic density.

Nat Rev Neurosci, 10, 87-99.

18172207 A.M.Ebert, C.A.McAnelly, A.Srinivasan, J.L.Linker, W.A.Horne, and D.M.Garrity (2008).
Ca2+ channel-independent requirement for MAGUK family CACNB4 genes in initiation of zebrafish epiboly.

Proc Natl Acad Sci U S A, 105, 198-203.

18419826 A.M.Ebert, C.A.McAnelly, A.Srinivasan, R.L.Mueller, D.B.Garrity, and D.M.Garrity (2008).
The calcium channel beta2 (CACNB2) subunit repertoire in teleosts.

BMC Mol Biol, 9, 38.

18682574 A.M.Ebert, C.A.McAnelly, A.V.Handschy, R.L.Mueller, W.A.Horne, and D.M.Garrity (2008).
Genomic organization, expression, and phylogenetic analysis of Ca2+ channel beta4 genes in 13 vertebrate species.

Physiol Genomics, 35, 133-144.

18535142 A.Ravindran, Q.Z.Lao, J.B.Harry, P.Abrahimi, E.Kobrinsky, and N.M.Soldatov (2008).
Calmodulin-dependent gating of Ca(v)1.2 calcium channels in the absence of Ca(v)beta subunits.

Proc Natl Acad Sci U S A, 105, 8154-8159.

17929154 A.Y.Kuznetsova, and R.C.Deth (2008).
A model for modulation of neuronal synchronization by D4 dopamine receptor-mediated phospholipid methylation.

J Comput Neurosci, 24, 314-329.

18339621 D.Jeon, I.Song, W.Guido, K.Kim, E.Kim, U.Oh, and H.S.Shin (2008).
Ablation of Ca2+ channel beta3 subunit leads to enhanced N-methyl-D-aspartate receptor-dependent long term potentiation and improved long term memory.

J Biol Chem, 283, 12093-12101.

18725532 G.Gonzalez-Gutierrez, E.Miranda-Laferte, D.Naranjo, P.Hidalgo, and A.Neely (2008).
Mutations of nonconserved residues within the calcium channel alpha1-interaction domain inhibit beta-subunit potentiation.

J Gen Physiol, 132, 383-395.

18776052 G.Gonzalez-Gutierrez, E.Miranda-Laferte, D.Nothmann, S.Schmidt, A.Neely, and P.Hidalgo (2008).
The guanylate kinase domain of the beta-subunit of voltage-gated calcium channels suffices to modulate gating.

Proc Natl Acad Sci U S A, 105, 14198-14203.

18958281 I.Vitko, A.Shcheglovitov, J.P.Baumgart, I.I.Arias-Olguín, J.Murbartián, J.M.Arias, and E.Perez-Reyes (2008).
Orientation of the calcium channel beta relative to the alpha(1)2.2 subunit is critical for its regulation of channel activity.

PLoS ONE, 3, e3560.

18628210 M.Murakami, T.Ohba, F.Xu, E.Satoh, I.Miyoshi, T.Suzuki, Y.Takahashi, E.Takahashi, H.Watanabe, K.Ono, H.Sasano, N.Kasai, H.Ito, and T.Iijima (2008).
Modified Sympathetic Nerve System Activity with Overexpression of the Voltage-dependent Calcium Channel {beta}3 Subunit.

J Biol Chem, 283, 24554-24560.

18411278 Q.Z.Lao, E.Kobrinsky, J.B.Harry, A.Ravindran, and N.M.Soldatov (2008).
New Determinant for the CaVbeta2 subunit modulation of the CaV1.2 calcium channel.

J Biol Chem, 283, 15577-15588.

17110381 G.Gonzalez-Gutierrez, E.Miranda-Laferte, A.Neely, and P.Hidalgo (2007).
The Src homology 3 domain of the beta-subunit of voltage-gated calcium channels promotes endocytosis via dynamin interaction.

J Biol Chem, 282, 2156-2162.

18001290 K.S.Richards, A.M.Swensen, D.Lipscombe, and K.Bommert (2007).
Novel CaV2.1 clone replicates many properties of Purkinje cell CaV2.1 current.

Eur J Neurosci, 26, 2950-2961.

17496037 L.L.He, Y.Zhang, Y.H.Chen, Y.Yamada, and J.Yang (2007).
Functional modularity of the beta-subunit of voltage-gated Ca2+ channels.

Biophys J, 93, 834-845.

17220895 M.L.Reese, S.Dakoji, D.S.Bredt, and V.Dötsch (2007).
The guanylate kinase domain of the MAGUK PSD-95 binds dynamically to a conserved motif in MAP1a.

Nat Struct Mol Biol, 14, 155-163.

17664337 M.Xie, X.Li, J.Han, D.L.Vogt, S.Wittemann, M.D.Mark, and S.Herlitze (2007).
Facilitation versus depression in cultured hippocampal neurons determined by targeting of Ca2+ channel Cavbeta4 versus Cavbeta2 subunits to synaptic terminals.

J Cell Biol, 178, 489-502.

17303572 P.Béguin, Y.J.Ng, C.Krause, R.N.Mahalakshmi, M.Y.Ng, and W.Hunziker (2007).
RGK small GTP-binding proteins interact with the nucleotide kinase domain of Ca2+-channel beta-subunits via an uncommon effector binding domain.

J Biol Chem, 282, 11509-11520.

17899404 R.A.Bannister (2007).
Bridging the myoplasmic gap: recent developments in skeletal muscle excitation-contraction coupling.

J Muscle Res Cell Motil, 28, 275-283.

17526524 Y.L.Lai, S.C.Yen, S.H.Yu, and J.K.Hwang (2007).
pKNOT: the protein KNOT web server.

Nucleic Acids Res, 35, W420-W424.

17028169 A.Badou, M.K.Jha, D.Matza, W.Z.Mehal, M.Freichel, V.Flockerzi, and R.A.Flavell (2006).
Critical role for the beta regulatory subunits of Cav channels in T lymphocyte function.

Proc Natl Acad Sci U S A, 103, 15529-15534.

16402121 A.C.Dolphin (2006).
A short history of voltage-gated calcium channels.

Br J Pharmacol, 147, S56-S62.

16385006 A.C.Vendel, C.D.Rithner, B.A.Lyons, and W.A.Horne (2006).
Solution structure of the N-terminal A domain of the human voltage-gated Ca2+channel beta4a subunit.

Protein Sci, 15, 378-383.

PDB code: 2d46

16627564 A.J.Butcher, J.Leroy, M.W.Richards, W.S.Pratt, and A.C.Dolphin (2006).
The importance of occupancy rather than affinity of CaV(beta) subunits for the calcium channel I-II linker in relation to calcium channel function.

J Physiol, 574, 387-398.

16706839 A.Sandoval, N.Oviedo, A.Tadmouri, T.Avila, M.De Waard, and R.Felix (2006).
Two PEST-like motifs regulate Ca2+/calpain-mediated cleavage of the CaVbeta3 subunit and provide important determinants for neuronal Ca2+ channel activity.

Eur J Neurosci, 23, 2311-2320.

16790445 B.S.Finlin, R.N.Correll, C.Pang, S.M.Crump, J.Satin, and D.A.Andres (2006).
Analysis of the complex between Ca2+ channel beta-subunit and the Rem GTPase.

J Biol Chem, 281, 23557-23566.

17074979 L.Seu, and G.S.Pitt (2006).
Dose-dependent and isoform-specific modulation of Ca2+ channels by RGK GTPases.

J Gen Physiol, 128, 605-613.

17057713 M.Pioletti, F.Findeisen, G.L.Hura, and D.L.Minor (2006).
Three-dimensional structure of the KChIP1-Kv4.3 T1 complex reveals a cross-shaped octamer.

Nat Struct Mol Biol, 13, 987-995.

PDB code: 2i2r

16801381 N.Kanevsky, and N.Dascal (2006).
Regulation of maximal open probability is a separable function of Ca(v)beta subunit in L-type Ca2+ channel, dependent on NH2 terminus of alpha1C (Ca(v)1.2alpha).

J Gen Physiol, 128, 15-36.

16317008 V.Leuranguer, S.Papadopoulos, and K.G.Beam (2006).
Organization of calcium channel beta1a subunits in triad junctions in skeletal muscle.

J Biol Chem, 281, 3521-3527.

16157588 A.Hohaus, S.Beyl, M.Kudrnac, S.Berjukow, E.N.Timin, R.Marksteiner, M.A.Maw, and S.Hering (2005).
Structural determinants of L-type channel activation in segment IIS6 revealed by a retinal disorder.

J Biol Chem, 280, 38471-38477.

16088377 B.E.Flucher, G.J.Obermair, P.Tuluc, J.Schredelseker, G.Kern, and M.Grabner (2005).
The role of auxiliary dihydropyridine receptor subunits in muscle.

J Muscle Res Cell Motil, 26, 1-6.

16299511 F.Van Petegem, F.C.Chatelain, and D.L.Minor (2005).
Insights into voltage-gated calcium channel regulation from the structure of the CaV1.2 IQ domain-Ca2+/calmodulin complex.

Nat Struct Mol Biol, 12, 1108-1115.

PDB code: 2be6

16322774 I.Bodi, G.Mikala, S.E.Koch, S.A.Akhter, and A.Schwartz (2005).
The L-type calcium channel in the heart: the beat goes on.

J Clin Invest, 115, 3306-3317.

15750602 J.M.Maltez, D.A.Nunziato, J.Kim, and G.S.Pitt (2005).
Essential Ca(V)beta modulatory properties are AID-independent.

Nat Struct Mol Biol, 12, 372-377.

16286639 J.Schredelseker, V.Di Biase, G.J.Obermair, E.T.Felder, B.E.Flucher, C.Franzini-Armstrong, and M.Grabner (2005).
The beta 1a subunit is essential for the assembly of dihydropyridine-receptor arrays in skeletal muscle.

Proc Natl Acad Sci U S A, 102, 17219-17224.

15507442 L.Berrou, Y.Dodier, A.Raybaud, A.Tousignant, O.Dafi, J.N.Pelletier, and L.Parent (2005).
The C-terminal residues in the alpha-interacting domain (AID) helix anchor CaV beta subunit interaction and modulation of CaV2.3 channels.

J Biol Chem, 280, 494-505.

15952887 L.Funke, S.Dakoji, and D.S.Bredt (2005).
Membrane-associated guanylate kinases regulate adhesion and plasticity at cell junctions.

Annu Rev Biochem, 74, 219-245.

15816172 R.J.French, and G.W.Zamponi (2005).
Voltage-gated sodium and calcium channels in nerve, muscle, and heart.

IEEE Trans Nanobioscience, 4, 58-69.

16569296 R.M.Greenberg (2005).
Ca2+ signalling, voltage-gated Ca2+ channels and praziquantel in flatworm neuromusculature.

Parasitology, 131, S97-108.

16020456 S.Dalton, S.X.Takahashi, J.Miriyala, and H.M.Colecraft (2005).
A single CaVbeta can reconstitute both trafficking and macroscopic conductance of voltage-dependent calcium channels.

J Physiol, 567, 757-769.

16186563 S.X.Takahashi, J.Miriyala, L.H.Tay, D.T.Yue, and H.M.Colecraft (2005).
A CaVbeta SH3/guanylate kinase domain interaction regulates multiple properties of voltage-gated Ca2+ channels.

J Gen Physiol, 126, 365-377.

16357209 W.Cheng, X.Altafaj, M.Ronjat, and R.Coronado (2005).
Interaction between the dihydropyridine receptor Ca2+ channel beta-subunit and ryanodine receptor type 1 strengthens excitation-contraction coupling.

Proc Natl Acad Sci U S A, 102, 19225-19230.

15627376 I.I.Serysheva (2004).
Structural insights into excitation-contraction coupling by electron cryomicroscopy.

Biochemistry (Mosc), 69, 1226-1232.

15339916 J.B.Harry, E.Kobrinsky, D.R.Abernethy, and N.M.Soldatov (2004).
New short splice variants of the human cardiac Cavbeta2 subunit: redefining the major functional motifs implemented in modulation of the Cav1.2 channel.

J Biol Chem, 279, 46367-46372.

15265869 J.D.Spafford, J.Van Minnen, P.Larsen, A.B.Smit, N.I.Syed, and G.W.Zamponi (2004).
Uncoupling of calcium channel alpha1 and beta subunits in developing neurons.

J Biol Chem, 279, 41157-41167.

15339810 O.Dafi, L.Berrou, Y.Dodier, A.Raybaud, R.Sauvé, and L.Parent (2004).
Negatively charged residues in the N-terminal of the AID helix confer slow voltage dependent inactivation gating to CaV1.2.

Biophys J, 87, 3181-3192.

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 codes are shown on the right.