3HKC

Tubulin-ABT751: RB3 stathmin-like domain complex

Summary for 3HKC

• Entry DOI: 10.2210/pdb3hkc/pdb
• Related: 1SA0 1SA1 3HKB 3HKD 3HKE
• Descriptor: Tubulin alpha chain, Tubulin beta chain, Stathmin-4, ... (7 entities in total)
• Functional Keywords: alpha-tubulin, beta-tubulin, colchicine domain, gtpase microtubule, stathmin, tubulin, cell cycle
• Biological source: Rattus norvegicus (rat); More
• Total number of polymer chains: 5
• Total formula weight: 219777.94

Authors

Dorleans, A.,Gigant, B.,Ravelli, R.B.G.,Mailliet, P.,Mikol, V.,Knossow, M. (deposition date: 2009-05-23, release date: 2009-09-01, Last modification date: 2023-11-01)

Primary citation

Dorleans, A.,Gigant, B.,Ravelli, R.B.G.,Mailliet, P.,Mikol, V.,Knossow, M.
Variations in the colchicine-binding domain provide insight into the structural switch of tubulin
Proc.Natl.Acad.Sci.USA, 106:13775-13779, 2009

PubMed Abstract: Structural changes occur in the alphabeta-tubulin heterodimer during the microtubule assembly/disassembly cycle. Their most prominent feature is a transition from a straight, microtubular structure to a curved structure. There is a broad range of small molecule compounds that disturbs the microtubule cycle, a class of which targets the colchicine-binding site and prevents microtubule assembly. This class includes compounds with very different chemical structures, and it is presently unknown whether they prevent tubulin polymerization by the same mechanism. To address this issue, we have determined the structures of tubulin complexed with a set of such ligands and show that they interfere with several of the movements of tubulin subunits structural elements upon its transition from curved to straight. We also determined the structure of tubulin unliganded at the colchicine site; this reveals that a beta-tubulin loop (termed T7) flips into this site. As with colchicine site ligands, this prevents a helix which is at the interface with alpha-tubulin from stacking onto a beta-tubulin beta sheet as in straight protofilaments. Whereas in the presence of these ligands the interference with microtubule assembly gets frozen, by flipping in and out the beta-subunit T7 loop participates in a reversible way in the resistance to straightening that opposes microtubule assembly. Our results suggest that it thereby contributes to microtubule dynamic instability.

PubMed: 19666559
DOI: 10.1073/pnas.0904223106

Experimental method

X-RAY DIFFRACTION (3.8 Å)