PDBsum entry 2w73

Metal binding protein

PDB id: 2w73

Contents

Protein chains

145 a.a. *

17 a.a. *

Metals

_CA ×20

Waters ×340

* Residue conservation analysis

PDB id:

2w73

Name:

Metal binding protein

Title:

High-resolution structure of the complex between calmodulin and a peptide from calcineurin a

Structure:

Calmodulin. Chain: a, b, e, f. Synonym: cam. Engineered: yes. Serine/threonine-protein phosphatase 2b catalytic subunit alpha isoform. Chain: k, l, m, o. Fragment: calmodulin binding domain, residues 385-411. Synonym: calmodulin-dependent calcineurin a subunit alpha isoform,

Source:

Homo sapiens. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.45Å R-factor: 0.187 R-free: 0.217

Authors:

V.Majava,P.Kursula

Key ref:

V.Majava and P.Kursula (2009). Domain swapping and different oligomeric States for the complex between calmodulin and the calmodulin-binding domain of calcineurin a. Plos One, 4, e5402. PubMed id: 19404396

Date:

19-Dec-08 Release date: 12-May-09

Protein chains

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 145 a.a.

Protein chains

Q08209  (PP2BA_HUMAN) -  Protein phosphatase 3 catalytic subunit alpha from Homo sapiens

Seq: 521 a.a.

Struc: 17 a.a.

Enzyme reactions

• Enzyme class: Chains K, L, M, O: E.C.3.1.3.16 - protein-serine/threonine phosphatase.
• Reaction:
  1. O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate
  2. O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Plos One 4:e5402 (2009)

PubMed id: 19404396

Domain swapping and different oligomeric States for the complex between calmodulin and the calmodulin-binding domain of calcineurin a.

V.Majava, P.Kursula.

ABSTRACT

BACKGROUND: Calmodulin (CaM) is a ubiquitously expressed calcium sensor that engages in regulatory interactions with a large number of cellular proteins. Previously, a unique mode of CaM target recognition has been observed in the crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A. METHODOLOGY/PRINCIPAL FINDINGS: We have solved a high-resolution crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A in a novel crystal form, which shows a dimeric assembly of calmodulin, as observed before in the crystal state. We note that the conformation of CaM in this complex is very similar to that of unliganded CaM, and a detailed analysis revels that the CaM-binding motif in calcineurin A is of a novel '1-11' type. However, using small-angle X-ray scattering (SAXS), we show that the complex is fully monomeric in solution, and a structure of a canonically collapsed CaM-peptide complex can easily be fitted into the SAXS data. This result is also supported by size exclusion chromatography, where the addition of the ligand peptide decreases the apparent size of CaM. In addition, we studied the energetics of binding by isothermal titration calorimetry and found them to closely resemble those observed previously for ligand peptides from CaM-dependent kinases. CONCLUSIONS/SIGNIFICANCE: Our results implicate that CaM can also form a complex with the CaM-binding domain of calcineurin in a 1 ratio 1 stoichiometry, in addition to the previously observed 2 ratio 2 arrangement in the crystal state. At the structural level, going from 2 ratio 2 association to two 1 ratio 1 complexes will require domain swapping in CaM, accompanied by the characteristic bending of the central linker helix between the two lobes of CaM.