1sa1
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TUBULIN-PODOPHYLLOTOXIN: STATHMIN-LIKE DOMAIN COMPLEX
OverviewOverview
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.
About this StructureAbout this Structure
1SA1 is a Protein complex structure of sequences from Bos taurus and Rattus norvegicus with MG, GTP, GDP and POD as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain., Ravelli RB, Gigant B, Curmi PA, Jourdain I, Lachkar S, Sobel A, Knossow M, Nature. 2004 Mar 11;428(6979):198-202. PMID:15014504
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