Title
Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single α Helix Lever Arm Extension
Author
Jianchao Li, Yiyun Chen, Yisong Deng, Ilona Christy Unarta, Qing Lu, Xuhui Huang, Mingjie Zhang
Year
2017
Journal
Structure
Abstract
Several unconventional myosins contain a highly charged single α helix (SAH) immediately following the calmodulin (CaM) binding IQ motifs, functioning to extend lever arms of these myosins. How such SAH is connected to the IQ motifs and whether the conformation of the IQ motifs-SAH segments are regulated by Ca2+ fluctuations are not known. Here, we demonstrate by solving its crystal structure that the predicted SAH of myosin VIIa (Myo7a) forms a stable SAH. The structure of Myo7a IQ5-SAH segment in complex with apo-CaM reveals that the SAH sequence can extend the length of the Myo7a lever arm. Although Ca2+-CaM remains bound to IQ5-SAH, the Ca2+-induced CaM binding mode change softens the conformation of the IQ5-SAH junction, revealing a Ca2+-induced lever arm flexibility change for Myo7a. We further demonstrate that the last IQ motif of several other myosins also binds to both apo- and Ca2+-CaM, suggesting a common Ca2+-induced conformational regulation mechanism.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Protein denaturation, Chemical stability, Biochemistry