Initiation Mechanism of Kinesin's Neck Linker Docking Process
Yi-Zhao Geng1,2, Hui Zhang2, Gang Lyu3, Qing Ji1,2,4**
1Institute of Biophysics, Hebei University of Technology, Tianjin 300401 2School of Science, Hebei University of Technology, Tianjin 300401 3Mathematical and Physical Science School, North China Electric Power University, Baoding 071003 4State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190
Abstract：The neck linker (NL) docking to the motor domain is the key force generation process of a kinesin motor. In the initiation step of NL docking the first three residues (LYS325, THR326 and ILE327 in 2KIN) of the NL must form an 'extra turn', thus the other parts of the NL could dock to the motor domain. How the extra turn is formed remains elusive. We investigate the extra turn formation mechanism using structure-based mechanical analysis via molecular dynamics simulation. We find that the motor head rotation induced by ATP binding first drives ILE327 to move towards a hydrophobic pocket on the motor domain. The driving force, together with the hydrophobic interaction of ILE327 with the hydrophobic pocket, then causes a clockwise rotation of THR326, breaks the locking of LYS325, and finally drives the extra turn formation. This extra turn formation mechanism provides a clear pathway from ATP binding to NL docking of kinesin.
2017, Vol. 34 
