3E22

Tubulin-colchicine-soblidotin: Stathmin-like domain complex

Summary for 3E22

• Entry DOI: 10.2210/pdb3e22/pdb
• Related: 1SA0 1Z2B 3DU7
• Descriptor: Tubulin alpha-1C chain, Tubulin beta-2B chain, Stathmin-4, ... (8 entities in total)
• Functional Keywords: alpha-tubulin, beta-tubulin, colchicine, gtpase, microtubule, soblidotin, stathmin, tubulin, cell cycle
• Biological source: RATTUS NORVEGICUS (rat); More
• Cellular location: Cytoplasm, cytoskeleton (By similarity): Q3ZCJ7 Q6B856
• Total number of polymer chains: 5
• Total formula weight: 220311.31

Authors

Cormier, A.,Marchand, M.,Ravelli, R.B.,Knossow, M.,Gigant, B. (deposition date: 2008-08-05, release date: 2008-10-21, Last modification date: 2023-11-01)

Primary citation

Cormier, A.,Marchand, M.,Ravelli, R.B.,Knossow, M.,Gigant, B.
Structural insight into the inhibition of tubulin by vinca domain peptide ligands
Embo Rep., 9:1101-1106, 2008

PubMed Abstract: The tubulin vinca domain is the target of widely different microtubule inhibitors that interfere with the binding of vinblastine. Although all these ligands inhibit the hydrolysis of GTP, they affect nucleotide exchange to variable extents. The structures of two vinca domain antimitotic peptides--phomopsin A and soblidotin (a dolastatin 10 analogue)--bound to tubulin in a complex with a stathmin-like domain show that their sites partly overlap with that of vinblastine and extend the definition of the vinca domain. The structural data, together with the biochemical results from the ligands we studied, highlight two main contributors in nucleotide exchange: the flexibility of the tubulin subunits' arrangement at their interfaces and the residues in the carboxy-terminal part of the beta-tubulin H6-H7 loop. The structures also highlight common features of the mechanisms by which vinca domain ligands favour curved tubulin assemblies and destabilize microtubules.

PubMed: 18787557
DOI: 10.1038/embor.2008.171

Experimental method

X-RAY DIFFRACTION (3.8 Å)