PDBsum entry 1a03

Calcium-binding protein

PDB id: 1a03

Contents

Protein chains

90 a.a. *

* Residue conservation analysis

PDB id:

1a03

Name:

Calcium-binding protein

Title:

The three-dimensional structure of ca2+-bound calcyclin: implications for ca2+-signal transduction by s100 proteins, nmr, 20 structures

Structure:

Calcyclin (rabbit, ca2+). Chain: a, b. Synonym: 2a9, cacy, s100a6, pra. Engineered: yes. Other_details: rabbit, ca2+

Source:

Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Cell_line: bl21. Organ: lung. Gene: r-s100a6. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell_line: bl21.

NMR struc:

20 models

Authors:

M.Sastry,R.R.Ketchem,O.Crescenzi,C.Weber,M.J.Lubienski,H.Hidaka, W.J.Chazin

Key ref:

M.Sastry et al. (1998). The three-dimensional structure of Ca(2+)-bound calcyclin: implications for Ca(2+)-signal transduction by S100 proteins. Structure, 6, 223-231. PubMed id: 9519412 DOI: 10.1016/S0969-2126(98)00023-9

Date:

08-Dec-97 Release date: 02-Mar-99

Protein chains

P30801  (S10A6_RABIT) -  Protein S100-A6 from Oryctolagus cuniculus

Seq: 90 a.a.

Struc: 90 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/S0969-2126(98)00023-9

Structure 6:223-231 (1998)

PubMed id: 9519412

The three-dimensional structure of Ca(2+)-bound calcyclin: implications for Ca(2+)-signal transduction by S100 proteins.

M.Sastry, R.R.Ketchem, O.Crescenzi, C.Weber, M.J.Lubienski, H.Hidaka, W.J.Chazin.

ABSTRACT

BACKGROUND: Calcyclin is a member of the S100 subfamily of EF-hand Ca(2+)-binding proteins. This protein has implied roles in the regulation of cell growth and division, exhibits deregulated expression in association with cell transformation, and is found in high abundance in certain breast cancer cell lines. The novel homodimeric structural motif first identified for apo calcyclin raised the possibility that S100 proteins recognize their targets in a manner that is distinctly different from that of the prototypical EF-hand Ca2+ sensor, calmodulin. The NMR solution structure of Ca(2+)-bound calcyclin has been determined in order to identify Ca(2+)-induced structural changes and to obtain insights into the mechanism of Ca(2+)-triggered target protein recognition. RESULTS: The three-dimensional structure of Ca(2+)-bound calcyclin was calculated with 1372 experimental constraints, and is represented by an ensemble of 20 structures that have a backbone root mean square deviation of 1.9 A for the eight helices. Ca(2+)-bound calcyclin has the same symmetric homodimeric fold as observed for the apo protein. The helical packing within the globular domains and the subunit interface also change little upon Ca2+ binding. A distinct homology was found between the Ca(2+)-bound states of the calcyclin subunit and the monomeric S100 protein calbindin D9k. CONCLUSIONS: Only very modest Ca(2+)-induced changes are observed in the structure of calcyclin, in sharp contrast to the domain-opening that occurs in calmodulin and related Ca(2+)-sensor proteins. Thus, calcyclin, and by inference other members of the S100 family, must have a different mode for transducing Ca2+ signals and recognizing target proteins. This proposal raises significant questions concerning the purported roles of S100 proteins as Ca2+ sensors.

Selected figure(s)

Figure 2.
Figure 2. Comparison of the three-dimensional structures of calcyclin and calbindin D[9k] in the Ca^2+-bound state. Overview of calbindin D[9k] (a) and the calcyclin subunit (b), highlighting the conserved residues in the hydrophobic core (cyan). The two structures were first overlaid by best-fit superposition of the backbone atoms of helices I, II and IV, then separated for viewing. (c) Stereo close-up view of the conserved hydrophobic residues at the interface between helices I and IV, showing the similarity in the packing of corresponding sidechains. The structures were overlaid by best-fit superposition of the backbone atoms of helices I and IV. Calbindin D[9k] is shown in yellow and calcyclin is in salmon; the sidechains are labeled for calcyclin only. The coordinates for calbindin D[9k] were obtained from the Brookhaven PDB (accession code 2BCB). (Figure prepared using Insight II [Version 95.0; MSI, San Diego].)

The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 223-231) copyright 1998.

Figure was selected by the author.