Locking Function of a Key Residue in Kinesin's Gating Mechanism
GENG Yi-Zhao1, ZHANG Hui2, JI Qing2,3**, YAN Shi-Wei1**
1College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 2School of Science, Hebei University of Technology, Tianjin 300401 3Institute of Biophysics, Hebei University of Technology, Tianjin 300401
Abstract：In kinesin's mechanochemical cycle, ATP's binding to the nucleotide-free leading head is exquisitely gated so that futile hydrolysis is effectively avoided. Experiments show that, when both kinesin heads bind to a microtubule, ATP cannot bind to kinesin's leading head when the neck linker (NL) of this head has a backward orientation. How NL's backward orientation is maintained needs understanding on a structural basis. By using steered molecular dynamics and mutation simulations, we investigate the backward-pointing conformation of the leading head's NL under different inter-head tensions. We find that the NL cannot keep in a strict backward orientation solely by the inter-head tension. LYS325 (amino acid sequence in 2KIN) has an assistant locking function which locks the NL and β0 to the β-domain. This locking function has an enhanced positive cooperation with the inter-head tension. When the inter-head tension is weakened, this locking function can be broken, resulting in a loose backward orientation of the NL. The difference between the strict and loose backward orientation of the NL might be a crucial factor in the gating mechanism. These results are consistent with relevant experiments and proposals.
. [J]. 中国物理快报, 2014, 31(04): 48702-048702.
GENG Yi-Zhao, ZHANG Hui, JI Qing, YAN Shi-Wei. Locking Function of a Key Residue in Kinesin's Gating Mechanism. Chin. Phys. Lett., 2014, 31(04): 48702-048702.
2014, Vol. 31 
