Do calmodulin binding IQ motifs have built-in capping domains?

Most calmodulin (CaM) targets are α-helices. It is not clear if CaM induces the adoption of an α-helix configuration to its targets or if those targets are selected as they spontaneously adopt an α-helical conformation. Other than an α-helix propensity, there is a great variety of CaM targets with little more in common. One exception to this rule is the IQ site that can be recognized in a number of targets, such as those ion channels belonging to the KCNQ family. Although there is negligible sequence similarity between the IQ motif and the docking site on SK2 channels, both adopt a similar three-dimensional disposition. The isolated SK2 target presents a pre-folded core region that becomes fully α-helical upon binding to CaM. The existence of this pre-folded state suggests the occurrence of capping within CaM targets. In this review, we examine the capping properties within the residues flanking this core domain, and relate known IQ motifs and capping.The Government of the Autonomous Community of the Basque Country (IT1165-19 and KK-2020/00110) and the Spanish Ministry of Science and Innovation (RTI2018-097839-B-100 to A.V. and PID2019-105488GB-I00 to A.B., A.L., and O.R.B.) and FEDER funds provided financial support for this work. A.M-M. is supported by predoctoral contracts from the Basque Government administered by University of the Basque Country.Peer reviewe