Why Calmodulin Has Two Lobes

Science's STKE  29 May 2001:
Vol. 2001, Issue 84, pp. tw6
DOI: 10.1126/stke.2001.84.tw6

The calcium-binding protein calmodulin (CaM) is thought to modulate the P/Q-type calcium channel of neurons in two ways: to facilitate and then to inhibit channel opening. DeMaria et al. have fleshed out the molecular details of this dual regulation and report that the two competing processes are accommodated by calcium binding to two different lobes of CaM. Calcium binding to the COOH-terminal lobe stimulated channel opening, whereas calcium binding to the NH2-terminal lobe inhibited channel activity in transfected cells. They also found that calcium-bound CaM exerted these effects through a region called IQ in the receptor's alpha subunit, and not a previously identified region called the CaM binding site. The authors further discovered that calcium-free CaM appears preassociated with the resting channel and this may facilitate a rapid response to calcium.

C. D. DeMaria, T. W. Soong, B. A. Alseikhan, R. S. Alvania, D. T. Yue, Calmodulin bifurcates the local Ca2+ signal that modulates P/Q-type Ca2+ channels. Nature 411: 484-489 (2001). [Online Journal]