title: Neck rotation and neck mimic docking in the noncatalytic Kar3-associated protein Vik1.
abstract: BACKGROUND
  Kar3Vik1 is a heterodimeric kinesin with one catalytic subunit (Kar3) and one noncatalytic subunit (Vik1).
  
  
  RESULTS
  Vik1 experiences conformational changes in regions analogous to the force-producing elements in catalytic kinesins.
  
  
  CONCLUSIONS
  A molecular mechanism by which Kar3 could trigger Vik1's release from microtubules was revealed.
  
  
  CONCLUSIONS
  These findings will serve as the prototype for understanding the motile mechanism of kinesin-14 motors in general. It is widely accepted that movement of kinesin motor proteins is accomplished by coupling ATP binding, hydrolysis, and product release to conformational changes in the microtubule-binding and force-generating elements of their motor domain. Therefore, understanding how the Saccharomyces cerevisiae proteins Cik1 and Vik1 are able to function as direct participants in movement of Kar3Cik1 and Kar3Vik1 kinesin complexes presents an interesting challenge given that their motor homology domain (MHD) cannot bind ATP. Our crystal structures of the Vik1 ortholog from Candida glabrata may provide insight into this mechanism by showing that its neck and neck mimic-like element can adopt several different conformations reminiscent of those observed in catalytic kinesins. We found that when the neck is α-helical and interacting with the MHD core, the C terminus of CgVik1 docks onto the central β-sheet similarly to the ATP-bound form of Ncd. Alternatively, when neck-core interactions are broken, the C terminus is disordered. Mutations designed to impair neck rotation, or some of the neck-MHD interactions, decreased microtubule gliding velocity and steady state ATPase rate of CgKar3Vik1 complexes significantly. These results strongly suggest that neck rotation and neck mimic docking in Vik1 and Cik1 may be a structural mechanism for communication with Kar3.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Da
authors.initials: D
authors.lastname: Duan
authors.forename: Zhimeng
authors.initials: Z
authors.lastname: Jia
authors.forename: Monika
authors.initials: M
authors.lastname: Joshi
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Brunton
authors.forename: Michelle
authors.initials: M
authors.lastname: Chan
authors.forename: Doran
authors.initials: D
authors.lastname: Drew
authors.forename: Darlene
authors.initials: D
authors.lastname: Davis
authors.forename: John S
authors.initials: JS
authors.lastname: Allingham
mesh_terms: D020134:Catalytic Domain; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008868:Microtubule Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C076025:CIK1 protein, S cerevisiae; D005656:Fungal Proteins; C063504:KAR3 protein, S cerevisiae; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; C119241:VIK1 protein, S cerevisiae; D016547:Kinesins