Document Detail


Neck rotation and neck mimic docking in the noncatalytic Kar3-associated protein Vik1.
MedLine Citation:
PMID:  23043140     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
CONCLUSION: A molecular mechanism by which Kar3 could trigger Vik1's release from microtubules was revealed.
SIGNIFICANCE: 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:
Da Duan; Zhimeng Jia; Monika Joshi; Jacqueline Brunton; Michelle Chan; Doran Drew; Darlene Davis; John S Allingham
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-07
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-27     Completed Date:  2013-02-28     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  40292-301     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
PDB/4GKP;  4GKQ;  4GKR
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MeSH Terms
Descriptor/Qualifier:
Catalytic Domain
Fungal Proteins / chemistry*,  genetics,  metabolism
Humans
Kinesin / metabolism
Microtubule Proteins / chemistry,  genetics,  metabolism
Microtubule-Associated Proteins / chemistry*,  genetics,  metabolism
Protein Binding
Protein Conformation
Saccharomyces cerevisiae / chemistry,  genetics,  metabolism*
Saccharomyces cerevisiae Proteins / chemistry*,  genetics,  metabolism
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/CIK1 protein, S cerevisiae; 0/Fungal Proteins; 0/KAR3 protein, S cerevisiae; 0/Microtubule Proteins; 0/Microtubule-Associated Proteins; 0/Saccharomyces cerevisiae Proteins; 0/VIK1 protein, S cerevisiae; EC 3.6.1.-/Kinesin
Comments/Corrections

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