J. Evenas et al., Dynamics of the transition between open and closed conformations in a calmodulin C-terminal domain mutant, STRUCTURE, 9(3), 2001, pp. 185-195
Background: Calmodulin is a ubiquitous Ca2+-activated regulator of cellular
processes in eukaryotes. The structures of the Ca2+-free (apo) and Ca2+-lo
aded states of calmodulin have revealed that Ca2+ binding is associated wit
h a transition in each of the two domains from a closed to an open conforma
tion that is central to target recognition. However, little is known about
the dynamics of this conformational switch.
Results: The dynamics of the transition between closed and open conformatio
ns in the Ca2+-loaded state of the E140Q mutant of the calmodulin C-termina
l domain were characterized under equilibrium conditions. The exchange time
constants (tau (ex)) measured for 42 residues range from 13 to 46 mus, wit
h a mean of 21 +/- 3 mus. The results suggest that tau (ex) varies signific
antly between different groups of residues and that residues with similar v
alues exhibit spatial proximity in the structures of apo and/or Ca2+-satura
ted wild-type calmodulin. Using data for one of these groups, we obtained a
n open population of p(o) = 0.50 +/- 0.17 and a closed --> open rate consta
nt of k(o) = (2.7 +/- 1.0) x 10(4) s(-1).
Conclusions: The conformational exchange dynamics appear to involve locally
collective processes that depend on the structural topology. Comparisons w
ith previous results indicate that similar processes occur in the wild-type
protein. The measured rates match the estimated Ca2+ off rate, suggesting
that Ca2+ release may be gated by the conformational dynamics. Structural i
nterpretation of estimated chemical shifts suggests a mechanism for ion rel
ease.