Structure of Calmodulin Bound to a Calcineurin Peptide: A New Way of Making an Old Binding Mode
Calcineurin is a calmodulin-binding protein in brain and the only serine/threonine protein phosphatase under the control of Ca{sup 2+}/calmodulin (CaM), which plays a critical role in coupling Ca{sup 2+} signals to cellular responses. CaM up-regulates the phosphatase activity of calcineurin by binding to the CaM-binding domain (CBD) of calcineurin subunit A. Here, we report crystal structural studies of CaM bound to a CBD peptide. The chimeric protein containing CaM and the CBD peptide forms an intimate homodimer, in which CaM displays a native-like extended conformation and the CBD peptide shows -helical structure. Unexpectedly, the N-terminal lobe from one CaM and the C-terminal lobe from the second molecule form a combined binding site to trap the peptide. Thus, the dimer provides two binding sites, each of which is reminiscent of the fully collapsed conformation of CaM commonly observed in complex with, for example, the myosin light chain kinase (MLCK) peptide. The interaction between the peptide and CaM is highly specific and similar to MLCK.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 914079
- Report Number(s):
- BNL-78647-2007-JA; BICHAW; TRN: US0801526
- Journal Information:
- Biochemistry, Vol. 45, Issue 3; ISSN 0006-2960
- Country of Publication:
- United States
- Language:
- English
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