PEPping Up the Calmodulin Response

Sci. STKE, 16 December 2003
Vol. 2003, Issue 213, p. tw484
DOI: 10.1126/stke.2132003tw484
Calcium

PEPping Up the Calmodulin Response

Changes in intracellular calcium concentration [Ca2+]i of varying amplitude, frequency, and durationprovide a signaling code that can be deciphered through the action of calcium-binding proteins such as calmodulin (CaM). Putkey et al. investigated the role of PEP-19, a member of a class of highly abundant small, neuronal proteins with IQ motifs (a motif found in CaM-binding proteins) and no known catalytic function. They found that PEP-19 accelerated the rate of Ca2+ association and dissociation from the CaM C domain, enabling this domain to respond to rapid fluctuations in [Ca2+]i. The authors measured changes in the fluorescence of Quin-2, a Ca2+-indicator dye, and of tyrosine, an endogenous marker of Ca2+ binding to the C domain, and discovered that PEP-19 accelerated Ca2+ dissociation from the C domain of free CaM 40- to 50-fold (Ca2+ dissociation from the N domain is too rapid to measure). The equilibrium binding affinity was unchanged, as determined by a competitive dye-binding assay, which indicated that the rate of Ca2+ association was also increased; this was confirmed by measuring changes in tyrosine fluorescence. PEP-19 also greatly enhanced the rate of Ca2+ dissociation from CaM bound to CaM-dependent protein kinase IIα. The authors used nuclear magnetic resonance to identify PEP-19 binding sites on the CaM C domain. Although binding to targets can modify CaM's Ca2+ affinity (by slowing the dissociation rate), PEP-19 enhanced the rates of Ca2+ association and dissociation, which enabled the C domain to respond to rapid Ca2+ signals and helped fine-tune the response to the Ca2+ signaling code.

J. A. Putkey, Q. Kleerekoper, T. R. Gaertner, M. N. Waxham, A new role for IQ motif proteins in regulating calmodulin function. J. Biol. Chem. 278, 49667-49670 (2003). [Abstract] [Full Text]

Citation:

PEPping Up the Calmodulin Response. Sci. STKE 2003, tw484 (2003).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882