PDBsum entry: 2dpk

Metal transport

PDB id: 2dpk

Contents

Protein chain

124 a.a. *

Ligands

GAI

EPE

Metals

_CA ×4

Waters ×17

* Residue conservation analysis

PDB id:

2dpk

Name:

Metal transport

Title:

The crystal structure of the primary ca2+ sensor of the na+/ca2+ exchanger

Structure:

Sodium/calcium exchanger 1. Chain: a. Fragment: ca2+ binding domain 1. Synonym: cbd1, na+/ca2+ exchange protein 1. Engineered: yes

Source:

Canis lupus familiaris. Dog. Organism_taxid: 9615. Strain: familiaris. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell: m15prep4.

Resolution:

2.50Å R-factor: 0.225 R-free: 0.284

Authors:

J.Abramson,M.Sawaya

Key ref:

D.A.Nicoll et al. (2006). The crystal structure of the primary Ca2+ sensor of the Na+/Ca2+ exchanger reveals a novel Ca2+ binding motif. J Biol Chem, 281, 21577-21581. PubMed id: 16774926 DOI: 10.1074/jbc.C600117200

Date:

12-May-06 Release date: 13-Jun-06

Protein chain

P23685  (NAC1_CANFA) -  Sodium/calcium exchanger 1

Seq: 970 a.a.

Struc: 124 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: integral to membrane (1 term)
• Biological process: cell communication (1 term)

DOI no: 10.1074/jbc.C600117200

J Biol Chem 281:21577-21581 (2006)

PubMed id: 16774926

The crystal structure of the primary Ca2+ sensor of the Na+/Ca2+ exchanger reveals a novel Ca2+ binding motif.

D.A.Nicoll, M.R.Sawaya, S.Kwon, D.Cascio, K.D.Philipson, J.Abramson.

ABSTRACT

The Na+/Ca2+ exchanger is a plasma membrane protein that regulates intracellular Ca2+ levels in cardiac myocytes. Transport activity is governed by Ca2+, and the primary Ca2+ sensor (CBD1) is located in a large cytoplasmic loop connecting two transmembrane helices. The binding of Ca2+ to the CBD1 sensory domain results in conformational changes that stimulate the exchanger to extrude Ca2+. Here, we present a crystal structure of CBD1 at 2.5A resolution, which reveals a novel Ca2+ binding site consisting of four Ca2+ ions arranged in a tight planar cluster. This intricate coordination pattern for a Ca2+ binding cluster is indicative of a highly sensitive Ca2+ sensor and may represent a general platform for Ca2+ sensing.

Selected figure(s)

Figure 2.
FIGURE 2. Structure of CBD1. a, ribbon representation of CBD1. The seven -strands are colored from the N terminus (N) in blue to the C terminus (C) in red in the same orientation as in Fig. 1. The four Ca^2+ ions are depicted as green spheres. b, stereo view of the Ca^2+ binding sites. The main chain is represented in blue. The four Ca^2+ ions and three water molecules are colored as green and red spheres, respectively. The side chain carbons and oxygens are yellow and red, respectively. Coordination to the Ca^2+ ions is represented by black dashed lines. c, secondary structure schematic of CBD1. The -strands are depicted as blue arrows labeled from A to G, and the residues involved in Ca^2+ binding are shown in red circles. The A and G strands are disrupted by a -bulge and a cis-proline, respectively, resulting in strands A' and G'. The red box around A' indicates a break in hydrogen bonding arrangement, which results in a parallel alignment with strand G'.

Figure 3.
FIGURE 3. Sequence alignment between CBD1 and a representative set of C[2] domains positioned around the two acidic segments. The two acidic segments located in CBD1 are underlined in green, and the residues coordinating Ca^2+ are shown in yellow background. Residues whose backbone carbonyl groups coordinate Ca^2+ ions are shown on a blue background. The blue arrows represent -strands E-F-G (CBD1), 6-7-8 (SYN1) and 5-6-7 (PLC1). CBD1 is the sequence of the primary Ca^2+ binding sensor of NCX (canine); SYNI is the sequence of the C[2]A domain of synaptotagmin I (rat); PLCI is the C[2] domain of phospholipase C (rat).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 21577-21581) copyright 2006.

Figures were selected by an automated process.