1SA1

Tubulin-podophyllotoxin: stathmin-like domain complex

Summary for 1SA1

• Entry DOI: 10.2210/pdb1sa1/pdb
• Related: 1SA0
• Descriptor: Tubulin alpha chain, Tubulin beta chain, Stathmin 4, ... (7 entities in total)
• Functional Keywords: alpha-tubulin, beta-tubulin, colchicine, gtpase, microtubule podophyllotoxin, stathmin, tubulin, cell cycle
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cytoplasm, cytoskeleton: P02550 P02554 P02554
• Total number of polymer chains: 5
• Total formula weight: 219665.38

Authors

Ravelli, R.B.,Gigant, B.,Curmi, P.A.,Jourdain, I.,Lachkar, S.,Sobel, A.,Knossow, M. (deposition date: 2004-02-06, release date: 2004-03-23, Last modification date: 2023-08-23)

Primary citation

Ravelli, R.B.,Gigant, B.,Curmi, P.A.,Jourdain, I.,Lachkar, S.,Sobel, A.,Knossow, M.
Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain.
Nature, 428:198-202, 2004

PubMed Abstract: 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.

PubMed: 15014504
DOI: 10.1038/nature02393

Experimental method

X-RAY DIFFRACTION (4.2 Å)