A coordinated molecular 'fishing' mechanism in heterodimeric kinesin.
Kar3 is a kinesin motor that facilitates chromosome segregation during cell division. Unlike many members of the kinesin superfamily, Kar3 forms a heterodimer with non-motor protein Vik1 or Cik1 in vivo. The heterodimers show ATP-driven minus-end directed motility along a microtubule (MT) lattice, and also serve as depolymerase at the MT ends. The molecular mechanisms behind this dual functionality remain mysterious. Here, a molecular mechanical model for the Kar3/Vik1 heterodimer based on structural, kinetic and motility data reveals a long-range chemomechanical transmission mechanism that resembles a familiar fishing tactic. By this molecular 'fishing', ATP-binding to Kar3 dissociates catalytically inactive Vik1 off MT to facilitate minus-end sliding of the dimer on the MT lattice. When the dimer binds the frayed ends of MT, the fishing channels ATP hydrolysis energy into MT depolymerization by a mechanochemical effect. The molecular fishing thus provides a unified mechanistic ground for Kar3's dual functionality. The fishing-promoted depolymerization differs from the depolymerase mechanisms found in homodimeric kinesins. The fishing also enables intermolecular coordination with a chemomechanical coupling feature different from the paradigmatic pattern of homodimeric motors. This study rationalizes some puzzling experimental observation, and suggests new experiments for further elucidation of the fishing mechanism.
Hou
Ruizheng
R
Department of Physics, NUS Graduate School for Integrative Sciences and Engineering, and Center for Computational Science & Engineering, National University of Singapore, Singapore.
Wang
Zhisong
Z
D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D016547:Kinesins / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization
D000255:Adenosine Triphosphate; D016547:Kinesins