Abstract:
:Among the multiple steps constituting the kinesin mechanochemical cycle, one of the most interesting events is observed when kinesins move an 8-nm step from one microtubule (MT)-binding site to another. The stepping motion that occurs within a relatively short time scale ( approximately 100 mus) is, however, beyond the resolution of current experiments. Therefore, a basic understanding to the real-time dynamics within the 8-nm step is still lacking. For instance, the rate of power stroke (or conformational change) that leads to the undocked-to-docked transition of neck-linker is not known, and the existence of a substep during the 8-nm step still remains a controversial issue in the kinesin community. By using explicit structures of the kinesin dimer and the MT consisting of 13 protofilaments, we study the stepping dynamics with varying rates of power stroke (k(p)). We estimate that k(p)(-1) less, similar 20 micros to avoid a substep in an averaged time trace. For a slow power stroke with k(p)(-1) > 20 micros, the averaged time trace shows a substep that implies the existence of a transient intermediate, which is reminiscent of a recent single-molecule experiment at high resolution. We identify the intermediate as a conformation in which the tethered head is trapped in the sideway binding site of the neighboring protofilament. We also find a partial unfolding (cracking) of the binding motifs occurring at the transition state ensemble along the pathways before binding between the kinesin and MT.
journal_name
Proc Natl Acad Sci U S Aauthors
Hyeon C,Onuchic JNdoi
10.1073/pnas.0708828104subject
Has Abstractpub_date
2007-10-30 00:00:00pages
17382-7issue
44eissn
0027-8424issn
1091-6490pii
0708828104journal_volume
104pub_type
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