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Title: Structure of Calmodulin Bound to a Calcineurin Peptide: A New Way of Making an Old Binding Mode

Abstract

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.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
914079
Report Number(s):
BNL-78647-2007-JA
Journal ID: ISSN 0006-2960; BICHAW; TRN: US0801526
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemistry; Journal Volume: 45; Journal Issue: 3
Country of Publication:
United States
Language:
English
Subject:
43 PARTICLE ACCELERATORS; BRAIN; CALMODULIN; CHAINS; DIMERS; MYOSIN; PEPTIDES; PHOSPHATASES; PROTEINS; NSLS; national synchrotron light source

Citation Formats

Ye,Q., Li, X., Wong, A., Wei, Q., and Jia, Z.. Structure of Calmodulin Bound to a Calcineurin Peptide: A New Way of Making an Old Binding Mode. United States: N. p., 2006. Web. doi:10.1021/bi0521801.
Ye,Q., Li, X., Wong, A., Wei, Q., & Jia, Z.. Structure of Calmodulin Bound to a Calcineurin Peptide: A New Way of Making an Old Binding Mode. United States. doi:10.1021/bi0521801.
Ye,Q., Li, X., Wong, A., Wei, Q., and Jia, Z.. Sun . "Structure of Calmodulin Bound to a Calcineurin Peptide: A New Way of Making an Old Binding Mode". United States. doi:10.1021/bi0521801.
@article{osti_914079,
title = {Structure of Calmodulin Bound to a Calcineurin Peptide: A New Way of Making an Old Binding Mode},
author = {Ye,Q. and Li, X. and Wong, A. and Wei, Q. and Jia, Z.},
abstractNote = {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.},
doi = {10.1021/bi0521801},
journal = {Biochemistry},
number = 3,
volume = 45,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 2006},
month = {Sun Jan 01 00:00:00 EST 2006}
}