PDBsum entry 2ccm

Signaling protein

PDB id: 2ccm

Contents

Protein chains

190 a.a. *

Metals

_CA ×6

Waters ×682

* Residue conservation analysis

PDB id:

2ccm

Name:

Signaling protein

Title:

X-ray structure of calexcitin from loligo pealeii at 1.8a

Structure:

Calexcitin. Chain: a, b. Engineered: yes

Source:

Loligo pealeii. Longfin squid. Organism_taxid: 6621. Tissue: optic lobe. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.80Å R-factor: 0.191 R-free: 0.249

Authors:

P.T.Erskine,G.D.E.Beaven,S.P.Wood,G.Fox,J.Vernon,K.P.Giese,J.B.Cooper

Key ref:

P.T.Erskine et al. (2006). Structure of the neuronal protein calexcitin suggests a mode of interaction in signalling pathways of learning and memory. J Mol Biol, 357, 1536-1547. PubMed id: 16497326 DOI: 10.1016/j.jmb.2006.01.083

Date:

16-Jan-06 Release date: 26-Jan-06

Protein chains

O76764  (O76764_DORPE) -  Calexcitin from Doryteuthis pealeii

Seq: 191 a.a.

Struc: 190 a.a.

DOI no: 10.1016/j.jmb.2006.01.083

J Mol Biol 357:1536-1547 (2006)

PubMed id: 16497326

Structure of the neuronal protein calexcitin suggests a mode of interaction in signalling pathways of learning and memory.

P.T.Erskine, G.D.Beaven, R.Hagan, I.S.Findlow, J.M.Werner, S.P.Wood, J.Vernon, K.P.Giese, G.Fox, J.B.Cooper.

ABSTRACT

The three-dimensional structure of the neuronal calcium-sensor protein calexcitin from Loligo pealei has been determined by X-ray analysis at a resolution of 1.8A. Calexcitin is up-regulated following Pavlovian conditioning and has been shown to regulate potassium channels and the ryanodine receptor. Thus, calexcitin is implicated in neuronal excitation and plasticity. The overall structure is predominantly helical and compact with a pronounced hydrophobic core between the N and C-terminal domains of the molecule. The structure consists of four EF-hand motifs although only the first three EF hands are involved in binding calcium ions; the C-terminal EF-hand lacks the amino acids required for calcium binding. The overall structure is quite similar to that of the sarcoplasmic calcium-binding protein from Amphioxus although the sequence identity is very low at 31%. The structure shows that the two amino acids of calexcitin phosphorylated by protein kinase C are close to the domain interface in three dimensions and thus phosphorylation is likely to regulate the opening of the domains that is probably required for binding to target proteins. There is evidence that calexcitin is a GTPase and the residues, which have been implicated by mutagenesis in its GTPase activity, are in a short but highly conserved region of 3(10) helix close to the C terminus. This helix resides in a large loop that is partly sandwiched between the N and C-terminal domains suggesting that GTP binding may also require or may cause domain opening. The structure possesses a pronounced electropositive crevice in the vicinity of the 3(10) helix, that might provide an initial docking site for the triphosphate group of GTP. These findings elucidate a number of the reported functions of calexcitin with implications for neuronal signalling.

Selected figure(s)

Figure 2.
Figure 2. The domain structure of calexcitin with the N-terminal domain shown in green and the C-terminal domain coloured brown. Thr61, one site of phosphorylation by protein kinase C, is shown in ball-and-stick representation in the foreground. The other phosphorylation site (Thr188) is close to the C-terminal end of the molecule (also at the domain interface) which is largely out of view on the far side of the molecule in this view.

Figure 3.
Figure 3. The first calcium-binding site in L. pealei calexcitin formed by the loop residues 23–34. The calcium ion is coloured grey. The 2F[o]−F[c] electron density at 1.8 Å resolution is contoured at 1.2σ and is coloured pale blue.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 357, 1536-1547) copyright 2006.

Figures were selected by an automated process.