A New Role for IQ Motif Proteins in Regulating Calmodulin Function

IQ motifs are found in diverse families of calmodulin (CaM)-binding proteins. Some of these, like PEP-19 and RC3, are highly abundant in neuronal tissues, but being devoid of catalytic activity, their biological roles are not understood. We hypothesized that these IQ motif proteins might have unique...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2003-12, Vol.278 (50), p.49667-49670
Main Authors: Putkey, John A., Kleerekoper, Quinn, Gaertner, Tara R., Waxham, M. Neal
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Binding Sites
Calcium - metabolism
Calcium - pharmacology
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Calmodulin - chemistry
Calmodulin - metabolism
Calmodulin - physiology
Cell Line
DNA, Complementary - metabolism
Humans
Kinetics
Magnetic Resonance Spectroscopy
Models, Molecular
Nerve Tissue Proteins - chemistry
Nerve Tissue Proteins - physiology
Neurons - metabolism
Protein Binding
Protein Structure, Tertiary
Recombinant Proteins - metabolism
Signal Transduction
Time Factors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:IQ motifs are found in diverse families of calmodulin (CaM)-binding proteins. Some of these, like PEP-19 and RC3, are highly abundant in neuronal tissues, but being devoid of catalytic activity, their biological roles are not understood. We hypothesized that these IQ motif proteins might have unique effects on the Ca2+ binding properties of CaM, since they bind to CaM in the presence or absence of Ca2+. Here we show that PEP-19 accelerates by 40 to 50-fold both the slow association and dissociation of Ca2+ from the C-domain of free CaM, and we identify the sites of interaction between CaM and PEP-19 using NMR. Importantly, we demonstrate that PEP-19 can also increase the rate of dissociation of Ca2+ from CaM when bound to intact CaM-dependent protein kinase II. Thus, PEP-19, and presumably similar members of the IQ family of proteins, has the potential to alter the Ca2+-binding dynamics of free CaM and CaM that is bound to other target proteins. Since Ca2+ binding to the C-domain of CaM is the rate-limiting step for activation of CaM-dependent enzymes, the data reveal a new concept of importance in understanding the temporal dynamics of Ca2+-dependent cell signaling.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.C300372200