PDBsum entry 1t3l

Transport protein

PDB id: 1t3l

Contents

Protein chains

306 a.a. *

17 a.a. *

Waters ×128

* Residue conservation analysis

PDB id:

1t3l

Name:

Transport protein

Title:

Structural analysis of the voltage-dependent calcium channel beta subunit functional core in complex with alpha1 interaction domain

Structure:

Dihydropyridine-sensitive l-type, calcium channel beta-2 subunit. Chain: a. Fragment: functional core (residues 25-422). Synonym: voltage-dependent calcium channel beta-2 subunit, cab2. Engineered: yes. Mutation: yes. Voltage-dependent l-type calcium channel alpha-1s subunit. Chain: b.

Source:

Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Gene: cacnb2, cacnlb2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence of the peptide is from oryctolagus cuniculus (rabbit) gene cacna1s.

Biol. unit:

Dimer (from PQS)

Resolution:

2.20Å R-factor: 0.226 R-free: 0.282

Authors:

Y.Opatowsky,C.-C.Chen,K.P.Campbell,J.A.Hirsch

Key ref:

Y.Opatowsky et al. (2004). Structural analysis of the voltage-dependent calcium channel beta subunit functional core and its complex with the alpha 1 interaction domain. Neuron, 42, 387-399. PubMed id: 15134636 DOI: 10.1016/S0896-6273(04)00250-8

Date:

27-Apr-04 Release date: 25-May-04

Protein chain

P54288  (CACB2_RABIT) -  Voltage-dependent L-type calcium channel subunit beta-2 from Oryctolagus cuniculus

Seq: 632 a.a.

Struc: 306 a.a.*

Protein chain

P07293  (CAC1S_RABIT) -  Voltage-dependent L-type calcium channel subunit alpha-1S from Oryctolagus cuniculus

Seq: 1873 a.a.

Struc: 17 a.a.

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1016/S0896-6273(04)00250-8

Neuron 42:387-399 (2004)

PubMed id: 15134636

Structural analysis of the voltage-dependent calcium channel beta subunit functional core and its complex with the alpha 1 interaction domain.

Y.Opatowsky, C.C.Chen, K.P.Campbell, J.A.Hirsch.

ABSTRACT

Voltage-dependent calcium channels (VDCC) are multiprotein assemblies that regulate the entry of extracellular calcium into electrically excitable cells and serve as signal transduction centers. The alpha1 subunit forms the membrane pore while the intracellular beta subunit is responsible for trafficking of the channel to the plasma membrane and modulation of its electrophysiological properties. Crystallographic analyses of a beta subunit functional core alone and in complex with a alpha1 interaction domain (AID) peptide, the primary binding site of beta to the alpha1 subunit, reveal that beta represents a novel member of the MAGUK protein family. The findings illustrate how the guanylate kinase fold has been fashioned into a protein-protein interaction module by alteration of one of its substrate sites. Combined results indicate that the AID peptide undergoes a helical transition in binding to beta. We outline the mechanistic implications for understanding the beta subunit's broad regulatory role of the VDCC, particularly via the AID.

Selected figure(s)

Figure 1.
Figure 1. Structure of VDCC β Functional Core in Complex with the AIDRibbon (A) and topology (B) diagrams of the VDCC β subunit functional core bound to the AID peptide. Domain I, domain II, and the AID are represented in red, blue, and green, respectively. The topology scheme for each domain was patterned and labeled after the relevant canonical motif.

Figure 3.
Figure 3. Superposition of VDCC β Functional Core with c-Crk SH3 Domain, GuK, and PSD-95(A) Stereo diagram of β domain I (red), superimposed with PSD-95 SH3 domain (1JXO) (blue) and c-Crk SH3 domain (1CKA) (green) with a bound proline-rich peptide (yellow).(B) β domain II (blue) superimposed with GuK (yellow). β domain II was superimposed with yeast Guk (1GKY) (top). The same perspective was used to compare the lid and core subdomains of the GuK fold from the AID-β complex and mouse GuK with bound ADP (1LVG) (bottom).(C) AID bound β (left) and PSD-95 (right) after superposition of β domain II and the PSD GuK domain. PSD was then translated horizontally. β domain I, domain II, and AID are red, blue, and green, respectively, while the PSD SH3 and GuK domains are cyan and yellow, respectively.

The above figures are reprinted by permission from Cell Press: Neuron (2004, 42, 387-399) copyright 2004.

Figures were selected by an automated process.