Calmodulin interactions with IQ peptides from voltage-dependent calcium channels.
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.
Black
D J
DJ
Department of Molecular Physiology and Biophysics, BCM 335, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
Halling
D Brent
DB
Mandich
David V
DV
Pedersen
Steen E
SE
Altschuld
Ruth A
RA
Hamilton
Susan L
SL
D000595:Amino Acid Sequence; D000634:Aminoquinolines / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014364:Tryptophan / Q000378:metabolism
D000634:Aminoquinolines; D015220:Calcium Channels; D002147:Calmodulin; D005456:Fluorescent Dyes; D010455:Peptides; D021122:Protein Subunits; D014364:Tryptophan; C035739:Quin2; D002118:Calcium