title: Neck-linker docking coordinates the kinetics of kinesin's heads.
abstract: Conventional kinesin is a two-headed homodimeric motor protein, which is able to walk along microtubules processively by hydrolyzing ATP. Its neck linkers, which connect the two motor domains and can undergo a docking/undocking transition, are widely believed to play the key role in the coordination of the chemical cycles of the two motor domains and, consequently, in force production and directional stepping. Although many experiments, often complemented with partial kinetic modeling of specific pathways, support this idea, the ultimate test of the viability of this hypothesis requires the construction of a complete kinetic model. Considering the two neck linkers as entropic springs that are allowed to dock to their head domains, and incorporating only the few most relevant kinetic and structural properties of the individual heads, we develop here the first, to our knowledge, detailed, thermodynamically consistent model of kinesin that can 1), explain the cooperation of the heads (including their gating mechanisms) during walking, and 2), reproduce much of the available experimental data (speed, dwell-time distribution, randomness, processivity, hydrolysis rate, etc.) under a wide range of conditions (nucleotide concentrations, loading force, neck-linker length and composition, etc.). Besides revealing the mechanism by which kinesin operates, our model also makes it possible to look into the experimentally inaccessible details of the mechanochemical cycle and predict how certain changes in the protein affect its motion.
authors.affiliation: Department of Biological Physics, Eötvös University, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Czövek
authors.forename: Gergely J
authors.initials: GJ
authors.lastname: Szöllosi
authors.forename: Imre
authors.initials: I
authors.lastname: Derényi
mesh_terms: D016547:Kinesins / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D055503:Protein Multimerization; D013816:Thermodynamics
chemical_list: D016547:Kinesins