Document Detail

Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain.
MedLine Citation:
PMID:  15014504     Owner:  NLM     Status:  MEDLINE    
Microtubules are cytoskeletal polymers of tubulin involved in many cellular functions. Their dynamic instability is controlled by numerous compounds and proteins, including colchicine and stathmin family proteins. The way in which microtubule instability is regulated at the molecular level has remained elusive, mainly because of the lack of appropriate structural data. Here, we present the structure, at 3.5 A resolution, of tubulin in complex with colchicine and with the stathmin-like domain (SLD) of RB3. It shows the interaction of RB3-SLD with two tubulin heterodimers in a curved complex capped by the SLD amino-terminal domain, which prevents the incorporation of the complexed tubulin into microtubules. A comparison with the structure of tubulin in protofilaments shows changes in the subunits of tubulin as it switches from its straight conformation to a curved one. These changes correlate with the loss of lateral contacts and provide a rationale for the rapid microtubule depolymerization characteristic of dynamic instability. Moreover, the tubulin-colchicine complex sheds light on the mechanism of colchicine's activity: we show that colchicine binds at a location where it prevents curved tubulin from adopting a straight structure, which inhibits assembly.
Raimond B G Ravelli; Benoît Gigant; Patrick A Curmi; Isabelle Jourdain; Sylvie Lachkar; André Sobel; Marcel Knossow
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  428     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-11     Completed Date:  2004-04-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  198-202     Citation Subset:  IM    
European Molecular Biology Laboratory (EMBL), Grenoble Outstation, 6 rue Jules Horowitz, BP 181, 38042 Grenoble Cedex 9, France.
Data Bank Information
Bank Name/Acc. No.:
PDB/1SA0;  1SA1
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MeSH Terms
Amino Acid Sequence
Binding Sites
Colchicine / chemistry*,  metabolism*,  pharmacology
Microtubule Proteins*
Models, Molecular
Molecular Sequence Data
Nerve Growth Factors / chemistry*,  metabolism*
Phosphoproteins / chemistry*
Protein Structure, Quaternary
Protein Structure, Tertiary
Protein Subunits
Tubulin / chemistry*,  metabolism*
Tubulin Modulators
Reg. No./Substance:
0/Microtubule Proteins; 0/Nerve Growth Factors; 0/Phosphoproteins; 0/Protein Subunits; 0/STMN4 protein, human; 0/Stathmin; 0/Tubulin; 0/Tubulin Modulators; 64-86-8/Colchicine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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