1. Locking Function of a Key Residue in Kinesin's Gating Mechanism.
- Author
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Yi-Zhao, Geng, Hui, Zhang, Qing, Ji, and Shi-Wei, Yan
- Subjects
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KINESIN , *MICROTUBULES , *HYDROLYSIS , *NUCLEOTIDES , *NUCLEIC acids spectra , *CONFORMATIONAL analysis , *AMINO acid sequence - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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