4Q5U

Structure of calmodulin bound to its recognition site from calcineurin

Summary for 4Q5U

• Entry DOI: 10.2210/pdb4q5u/pdb
• Descriptor: Calmodulin, Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: ef hand, calcium binding protein-protein binding complex, calcium binding protein/protein binding
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, cytoskeleton, spindle: P62158; Cell membrane (By similarity): Q08209
• Total number of polymer chains: 2
• Total formula weight: 19833.35

Authors

Guo, H.,Dunlap, T.B.,Creamer, T.P.,Vander Kooi, C.W. (deposition date: 2014-04-17, release date: 2014-09-03, Last modification date: 2023-09-20)

Primary citation

Dunlap, T.B.,Guo, H.F.,Cook, E.C.,Holbrook, E.,Rumi-Masante, J.,Lester, T.E.,Colbert, C.L.,Vander Kooi, C.W.,Creamer, T.P.
Stoichiometry of the calcineurin regulatory domain-calmodulin complex.
Biochemistry, 53:5779-5790, 2014

PubMed 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 Å 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.

PubMed: 25144868
DOI: 10.1021/bi5004734

Experimental method

X-RAY DIFFRACTION (1.95 Å)