PDBsum entry 1ahr

Calcium-binding protein

PDB id: 1ahr

Contents

Protein chain

146 a.a. *

Metals

_CA ×4

Waters ×113

* Residue conservation analysis

PDB id:

1ahr

Name:

Calcium-binding protein

Title:

Calmodulin mutant with a two residue deletion in the central helix

Structure:

Calmodulin. Chain: a. Engineered: yes. Mutation: yes

Source:

Gallus gallus. Chicken. Organism_taxid: 9031. Cell_line: 293. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.80Å R-factor: 0.211

Authors:

L.Tabernero,J.Sack

Key ref:

L.Tabernero et al. (1997). The structure of a calmodulin mutant with a deletion in the central helix: implications for molecular recognition and protein binding. Structure, 5, 613-622. PubMed id: 9195880 DOI: 10.1016/S0969-2126(97)00217-7

Date:

10-Apr-97 Release date: 16-Jun-97

Protein chain

P62149  (CALM_CHICK) -  Calmodulin from Gallus gallus

Seq: 149 a.a.

Struc: 146 a.a.*

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

DOI no: 10.1016/S0969-2126(97)00217-7

Structure 5:613-622 (1997)

PubMed id: 9195880

The structure of a calmodulin mutant with a deletion in the central helix: implications for molecular recognition and protein binding.

L.Tabernero, D.A.Taylor, R.J.Chandross, M.F.VanBerkum, A.R.Means, F.A.Quiocho, J.S.Sack.

ABSTRACT

BACKGROUND: Calmodulin (CaM) is the major calcium-dependent regulator of a large variety of important intracellular processes in eukaryotes. The structure of CaM consists of two globular calcium-binding domains joined by a central 28-residue alpha helix. This linker helix has been hypothesized to act as a flexible tether and is crucial for the binding and activation of numerous target proteins. Although the way in which alterations of the central helix modulate the molecular recognition mechanism is not known exactly, the relative orientation of the globular domains seems to be of great importance. The structural analysis of central helix mutants may contribute to a better understanding of how changes in the conformation of CaM effect its function. RESULTS: We have determined the crystal structure of a calcium-saturated mutant of chicken CaM (mut-2) that lacks two residues in the central helix, Thr79 and Asp80, at 1.8 A resolution. The mutated shorter central helix is straight, relative to that of the wild-type structure. The loss of a partial turn of the central alpha helix causes the C-terminal domain to rotate 220 degrees around the helix axis, with respect to the N-terminal domain. This rotation places the two domains on the same side of the central helix, in a cis orientation, rather than in the trans orientation found in wild-type structures. CONCLUSIONS: The deletion of two residues in the central helix of CaM does not distort or cause a bending of the linker alpha helix. The main consequence of the mutation is a change in the relative orientation of the two globular calcium-binding domains, causing the hydrophobic patches in these domains to be closer and much less accessible to interact with the target enzymes. This may explain why this mutant of CaM shows a marked decrease in its ability to activate some enzymes while the mutation has little or no effect on its ability to activate others.

Selected figure(s)

Figure 1.
Figure 1. A comparison of wild type and mutant CaM. (a) Ribbon representation of Drosophila melanogaster native CaM (left) and mut-2 CaM (right). The region lost in the central helix deletion (residues 79-80) is colored in red and the residues surrounding the mutation (Asp 78 and Ser81) are represented by their Ca carbons in solid spheres; calcium ions are shown as black spheres. (Figure prepared using the program MOLSCRIPT [36].) (b) Helical wheel plots of the central helices of Drosophila melanogaster native CaM (4cln) and mut-2 CaM. Charged residues are shown in red, hydroxylated residues are shown in blue and nonpolar residues are shown in blue and nonpolar residues are shown in green. (Plot prepared using the program MolView [37].)

The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 613-622) copyright 1997.

Figure was selected by an automated process.