Key result
The mutant Cg1 bound Ca2+-calmodulin with 1/7th the affinity of 658C or whole caldesmon, and Ca2+-calmodulin was unable to reverse the Cg1-induced inhibition.
The interaction of calmodulin with the specific caldesmon sequence is crucial for reversing caldesmon inhibition of actin-tropomyosin activation of myosin ATPase.
Confirms sequence dependence of calmodulin-caldesmon interaction in vitro; leaves open relevance to cardiovascular smooth muscle regulation.
We have investigated the functional properties of a mutant (Cg1) derived from the C-terminal 99 amino acids of chicken caldesmon, 658-756 (658C) where the sequence 691glu-trp-leu-thr-lys-thr696 is changed to pro-gly-his-tyr-asn-asn. Cg1 bound Ca2+-calmodulin with (1/7)th of the affinity as compared to 658C or whole caldesmon. NMR titrations indicate that the contacts of Ca2+-calmodulin with the Trp-722 region of the peptide are retained but that those at the mutated site are lost. Most importantly Ca2+-calmodulin is not able to reverse the Cg1-induced inhibition. We conclude that the interaction of calmodulin with this caldesmon sequence is crucial for the reversal of caldesmon inhibition of actin-tropomyosin activation of myosin ATPase. The results are interpreted in terms of multisite attachment of actin and Ca2+-calmodulin to overlapping sequences in caldesmon domain 4b.
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Huber et al. (1998) studied this question. Mutant Cg1 (chicken caldesmon 658-756 with mutated sequence) vs. 658C or whole caldesmon was evaluated on Ca2+-calmodulin binding affinity and reversal of inhibition. The mutant Cg1 bound Ca2+-calmodulin with 1/7th the affinity of 658C or whole caldesmon, and Ca2+-calmodulin was unable to reverse the Cg1-induced inhibition.
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