Crystal structure of kinesin regulated by Ca(2+)-calmodulin.
Kinesins orchestrate cell division by controlling placement of chromosomes. Kinesins must be precisely regulated or else cell division fails. Calcium, a universal second messenger in eukaryotes, and calmodulin regulate some kinesins by causing the motor to dissociate from its biological track, the microtubule. Our focus was the mechanism of calcium regulation of kinesin at atomic resolution. Here we report the crystal structure of kinesin-like calmodulin-binding protein (KCBP) from potato, which was resolved to 2.3 A. The structure reveals three subdomains of the regulatory machinery located at the C terminus extension of the kinesin motor. Calmodulin that is activated by Ca2+ ions binds to an alpha-helix positioned on the microtubule-binding face of kinesin. A negatively charged segment following this helix competes with microtubules. A mimic of the conventional kinesin neck, connecting the calmodulin-binding helix to the KCBP motor core, links the regulatory machine to the kinesin catalytic cycle. Together with biochemical data, the crystal structure suggests that Ca(2+)-calmodulin inhibits the binding of KCBP to microtubules by blocking the microtubule-binding sites on KCBP.
Vinogradova
Maia V
MV
Department of Biochemistry/Biophysics, University of California, San Francisco, California 94143-2240, USA.
Reddy
Vaka S
VS
Reddy
Anireddy S N
AS
Sablin
Elena P
EP
Fletterick
Robert J
RJ
D029681:Arabidopsis Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D016547:Kinesins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D011198:Solanum tuberosum / Q000737:chemistry / Q000378:metabolism
D029681:Arabidopsis Proteins; D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; C099551:KCBP protein, Arabidopsis; D010940:Plant Proteins; D016547:Kinesins