IBM and NeSC workshop on Protein Science
National e-Science Centre, Edinburgh, March
15-16 2002
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Two heptamers of Mycobacterium tuberculosis chaperonin
10 self-associate through loop sequences active in bone resorption: a potential
cause of spinal tuberculosis Michael M Roberts(a), Alun R Coker(b), Gianluca Fossati(c), Paolo Mascagni(c), Anthony R M Coates(a) and Steve P Wood(b) (a) Department of Medical Microbiology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, England. (b) bDivision of Biochemistry and Molecular Biology, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, England. (c) Italfarmaco research Center, Via dei Lavoratori 54, 20092 Cinisello Balsamo, Milan, Italy. Chaperonin 10 (cpn10) is a 10kDa protein that acts together with cpn60 to catalyse protein folding in vivo. Binding of cpn10 to cpn60 occurs via a flexible loop on cpn10. This cpn10 loop was also shown to have bone-resorption activity1. We have determined the X-ray structure of M. tuberculosis cpn10 (mtcpn10) to 2.8 Å resolution2. This shows that two mtcpn10 heptamers, each a hollow dome-shaped structure with an opening at the top, are joined by interleaving flexible loop sequences at amino acid residues 17-35 to give a hollow spherical assembly 8.5 nm in diameter with an 8 Å opening at each end. Each mtcpn10 subunit has a ß-barrel structure that extends across the subunit interfaces. Electron density in the central hollow cavity suggests the encapsulation of protein and a possible role for this 14-mer in protein folding or transport. The conformation of the active loop sequences will be described as a possible route to defining the bone resorption receptor. |
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