Document Detail


Modulation of kinesin binding by the C-termini of tubulin.
MedLine Citation:
PMID:  14976555     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The flexible tubulin C-terminal tails (CTTs) have recently been implicated in the walking mechanism of dynein and kinesin. To address their role in the case of conventional kinesin, we examined the structure of kinesin-microtubule (MT) complexes before and after CTT cleavage by subtilisin. Our results show that the CTTs directly modulate the motor-tubulin interface and the binding properties of motors. CTT cleavage increases motor binding stability, and kinesin appears to adopt a binding conformation close to the nucleotide-free configuration under most nucleotide conditions. Moreover, C-terminal cleavage results in trapping a transient motor-ADP-MT intermediate. Using SH3-tagged dimeric and monomeric constructs, we could also show that the position of the kinesin neck is not affected by the C-terminal segments of tubulin. Overall, our study reveals that the tubulin C-termini define the stability of the MT-kinesin complex in a nucleotide-dependent manner, and highlights the involvement of tubulin in the regulation of weak and strong kinesin binding states.
Authors:
Georgios Skiniotis; Jared C Cochran; Jens Müller; Eckhard Mandelkow; Susan P Gilbert; Andreas Hoenger
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Publication Detail:
Type:  Journal Article     Date:  2004-02-19
Journal Detail:
Title:  The EMBO journal     Volume:  23     ISSN:  0261-4189     ISO Abbreviation:  EMBO J.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-10     Completed Date:  2005-06-20     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  989-99     Citation Subset:  IM    
Affiliation:
European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Diphosphate / metabolism,  pharmacology
Adenylyl Imidodiphosphate / metabolism,  pharmacology
Animals
Cattle
Dimerization
Kinesin / chemistry,  metabolism*
Kinetics
Microtubules / metabolism
Models, Molecular
Pliability
Protein Binding / drug effects
Protein Structure, Tertiary
Tubulin / chemistry*,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
K02 AR047841-02/AR/NIAMS NIH HHS; R01 GM054141-08/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Tubulin; 25612-73-1/Adenylyl Imidodiphosphate; 58-64-0/Adenosine Diphosphate; EC 3.6.1.-/Kinesin
Comments/Corrections

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