Calmodulin interactions with IQ peptides from voltage-dependent calcium channels

Am J Physiol Cell Physiol. 2005 Mar;288(3):C669-76. doi: 10.1152/ajpcell.00191.2004. Epub 2004 Oct 20.


Calmodulin (CaM) functions as a Ca(2+) sensor for inactivation and, in some cases, facilitation of a variety of voltage-dependent Ca(2+) 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 Ca(2+) channels increases the Ca(2+) affinity of both lobes of CaM, producing similar N- and C-lobe Ca(2+) affinities. Ca(2+) 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 Ca(2+) affinity and the most rapid rates of Ca(2+) association at both lobes, which is likely to make Ca(2+) binding to CaM, bound to this channel, less sensitive than other channels to intracellular Ca(2+) buffers. These kinetic differences in Ca(2+) 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 Ca(2+) channels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence*
  • Aminoquinolines / metabolism
  • Animals
  • Calcium / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calmodulin / chemistry
  • Calmodulin / genetics
  • Calmodulin / metabolism*
  • Cattle
  • Fluorescent Dyes / metabolism
  • Humans
  • Molecular Sequence Data
  • Peptides / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Sequence Alignment
  • Tryptophan / metabolism


  • Aminoquinolines
  • Calcium Channels
  • Calmodulin
  • Fluorescent Dyes
  • Peptides
  • Protein Subunits
  • Tryptophan
  • Quin2
  • Calcium