4Q5U: Structure Of Calmodulin Bound To Its Recognition Site From Calcineurin

Citation:
Abstract
Calcineurin is an essential serine/threonine phosphatase that plays vital roles in neuronal development and function, heart growth, and immune system activation. Calcineurin is unique in that it is the only phosphatase known to be activated by calmodulin in response to increasing intracellular calcium concentrations. Calcium-loaded calmodulin binds to the regulatory domain of calcineurin, resulting in a conformational change that removes an autoinhibitory domain from the active site of the phosphatase. We have determined a 1.95 A crystal structure of calmodulin bound to a peptide corresponding to its binding region from calcineurin. In contrast to previous structures of this complex, our structure has a stoichiometry of 1:1 and has the canonical collapsed, wraparound conformation observed for many calmodulin-substrate complexes. In addition, we have used size-exclusion chromatography and time-resolved fluorescence to probe the stoichiometry of binding of calmodulin to a construct corresponding to almost the entire regulatory domain from calcineurin, again finding a 1:1 complex. Taken in sum, our data strongly suggest that a single calmodulin protein is necessary and sufficient to bind to and activate each calcineurin enzyme.
PDB ID: 4Q5UDownload
MMDB ID: 122907
PDB Deposition Date: 2014/4/17
Updated in MMDB: 2014/09
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit for 4Q5U: dimeric; determined by author and by software (PISA)
Molecular Components in 4Q5U
Label Count Molecule
Proteins (2 molecules)
1
Calmodulin
Molecule annotation
1
Serine/threonine-protein Phosphatase 2B Catalytic Subunit Alpha Isoform(Gene symbol: PPP3CA)
Molecule annotation
Chemicals (4 molecules)
1
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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