Calmodulin interactions with IQ peptides from voltage-dependent calcium channels

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Abstract
Calmodulin (CaM) functions as a Ca2+ sensor for inactivation and, in some cases, facilitation of a variety of voltage-dependent Ca2+ channels. A crucial determinant for CaM binding to these channels is the IQ motif in the COOH-terminal tail of the channel-forming subunit. The binding of CaM to IQ peptides from Lc-, P/Q-, and R-type, but not N-type, voltage-dependent Ca2+ channels increases the Ca2+ affinity of both lobes of CaM, producing similar N- and C-lobe Ca2+ affinities. Ca2+ associates with and dissociates from the N-lobe much more rapidly than the C-lobe when CaM is bound to the IQ peptides. Compared with the other IQ peptides, CaM-bound Lc-IQ has the highest Ca2+ affinity and the most rapid rates of Ca2+ association at both lobes, which is likely to make Ca2+ binding to CaM, bound to this channel, less sensitive than other channels to intracellular Ca2+ buffers. These kinetic differences in Ca2+ binding to the lobes of CaM when bound to the different IQ motifs may explain both the ability of CaM to perform multiple functions in these channels and the differences in CaM regulation of the different voltage-dependent Ca2+ channels.