4IL1: Crystal Structure Of The Rat Calcineurin

Calcineurin is the only known calmodulin (CaM) activated protein phosphatase, which is involved in the regulation of numerous cellular and developmental processes and in calcium-dependent signal transduction. Although commonly assumed that CaM displaces the autoinhibitory domain (AID) blocking substrate access to its active site, the structural basis underlying activation remains elusive. We have created a fused ternary complex (CBA) by covalently linking three polypeptides: CaM, calcineurin regulatory B subunit (CnB) and calcineurin catalytic A subunit (CnA). CBA catalytic activity is comparable to that of fully activated native calcineurin in the presence of CaM. The crystal structure showed virtually no structural change in the active site and no evidence of CaM despite being covalently linked. The asymmetric unit contains four molecules; two parallel CBA pairs are packed in an antiparallel mode and the large cavities in crystal packing near the calcineurin active site would easily accommodate multiple positions of AID-bound CaM. Intriguingly, the conformation of the ordered segment of AID is not altered by CaM; thus, it is the disordered part of AID, which resumes a regular alpha-helical conformation upon binding to CaM, which is displaced by CaM for activation. We propose that the structural basis of calcineurin activation by CaM is through displacement of the disordered fragment of AID which otherwise impedes active site access.
PDB ID: 4IL1Download
MMDB ID: 114150
PDB Deposition Date: 2012/12/28
Updated in MMDB: 2013/10
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 4IL1: monomeric; determined by author and by software (PISA)
Molecular Components in 4IL1
Label Count Molecule
Protein (1 molecule)
Calmodulin, Calcineurin Subunit B Type 1, Serine/threonine- Protein Phosphatase 2B Catalytic Subunit Alpha Isoform
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB