In Calmodulin-IQ Domain Complexes, the Ca super(2+)-Free and Ca super(2+)-Bound Forms of the Calmodulin C-Lobe Direct the N-Lobe to Different Binding Sites

• Published in: Biochemistry (Easton) 2011-11, Vol.50 (46), p.10061-10068-10061-10068
• Main Authors: Black, D J, Persechini, Anthony
• Format: Article
• Language: English
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi201300v

We have investigated the roles played by the calmodulin (CaM) N- and C-lobes in establishing the conformations of CaM-IQ domain complexes in different Ca super(2+)-free and Ca super(2+)-bound states. Our results indicate a dominant role for the C-lobe in these complexes. When the C-lobe is Ca super(2+)-free, it directs the N-lobe to a binding site within the IQ domain consensus sequence. It appears that the N-lobe must be Ca super(2+)-free to interact productively with this site. When the C-lobe is Ca super(2+)-bound, it directs the N-lobe to a site upstream of the consensus sequence, and it appears that the N-lobe must be Ca super(2+)-bound to interact productively with this site. A model for switching in CaM-IQ domain complexes is presented in which the N-lobe adopts bound and extended positions that depend on the status of the Ca super(2+)-binding sites in each CaM lobe and the compositions of the two N-lobe binding sites. Ca super(2+)-dependent changes in the conformation of the bound C-lobe that appear to be responsible for directed N-lobe binding are also identified. Changes in the equilibria between extended and bound N-lobe positions may control bridging interactions in which the extended N-lobe is bound to another CaM-binding domain. Ca super(2+)-dependent control of bridging interactions with CaM has been implicated in the regulation of ion channel and unconventional myosin activities.