Document Detail

Computational and site-specific mutagenesis analyses of the asymmetric charge distribution on calmodulin.
MedLine Citation:
PMID:  2558379     Owner:  NLM     Status:  MEDLINE    
Calmodulin's calculated electrostatic potential surface is asymmetrically distributed about the molecule. Concentrations of uncompensated negative charge are localized near certain alpha-helices and calcium-binding loops. Further calculations suggest that these charge features of calmodulin can be selectively perturbed by changing clusters of phylogenetically conserved acidic amino acids in helices to lysines. When these cluster charge reversals are actually produced by using cassette-based site-specific mutagenesis of residues 82-84 or 118-120, the resulting proteins differ in their interaction with two distinct calmodulin-dependent protein kinases, myosin light chain kinase and calmodulin-dependent protein kinase II. Each calmodulin mutant can be purified to apparent chemical homogeneity by an identical purification protocol that is based on conservation of its overall properties, including calcium binding. Although cluster charge reversals result in localized perturbations of the computed negative surface, single amino acid changes would not be expected to alter significantly the distribution of the negative surface because of the relatively high density of uncompensated negative charge in the region around residues 82-84 and 118-120. However, this does not preclude the possibility of single amino acid charge perturbations having a functional effect on the more intimate, catalytically active complex. The electrostatic surface of calmodulin described in this report may be a feature that would be altered only by cluster charge reversal mutations. Overall, the results suggest that the charge properties of calmodulin are one of several properties that are important for the efficient assembly of calmodulin-protein kinase signal transduction complexes in eukaryotic cells.
P C Weber; T J Lukas; T A Craig; E Wilson; M M King; A P Kwiatkowski; D M Watterson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proteins     Volume:  6     ISSN:  0887-3585     ISO Abbreviation:  Proteins     Publication Date:  1989  
Date Detail:
Created Date:  1990-02-22     Completed Date:  1990-02-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8700181     Medline TA:  Proteins     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  70-85     Citation Subset:  IM    
Central Research and Development Department, E.I. du Pont de Nemours Co., Wilmington, Delaware 19880-0228.
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MeSH Terms
Amino Acid Sequence
Calcium-Calmodulin-Dependent Protein Kinases
Calmodulin* / genetics,  isolation & purification,  metabolism
Chemistry, Physical
Models, Molecular
Molecular Sequence Data
Myosin-Light-Chain Kinase / metabolism
Physicochemical Phenomena
Protein Conformation
Protein Kinases / metabolism
Signal Transduction
Grant Support
Reg. No./Substance:
0/Calmodulin; EC 2.7.-/Protein Kinases; EC Protein Kinases; EC Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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