CRYSTAL STRUCTURE OF THE IMMUNODOMINANT CHAPERONIN-10 OF MYCOBACTERIUM LEPRAE. Shekhar C. Mandea,*, Vijay Mehrab, Barry R. Bloomb,c and Wim G. J. Hold. aInstitute of Microbial Technology, Chandigarh 160 036, India; bDepartment of Microbiology and Immunology, and cHoward Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, New York, USA; and dBiomolecular Structure Centre and the Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195 USA.
Mycobacteria are amongst the most important human pathogens. In an effort to understand the immune response to mycobacterial infections, several antigens of these microbes have been identified. A 10kD antigen has been found to be the most immunogenic protein antigen of M.leprae. Interestingly it shares ~44% sequence identity with the well known chaperonin GroES of E. coli (1). We present the three dimensional structure of this protein, with possible hypothesis on the role of cpn-10 in the chaperonin mediated protein folding process.
The heptameric molecule has a dome like structure, with approximate dimensions of 80x80x35 angstroms (2). The overall architecture is strikingly similar to the pantheon in Rome. Residues important for its interaction with the larger chaperonin partner, cpn-60 (GroEL homologues) are sequestered on the lower surface of the dome. The interior of the dome is intensely hydrophilic. Residues lining the interior surface of the dome are conserved evolutionarily suggesting that GroES may take an active part in chaperonin mediated protein folding process.
(1) Mehra V et al., J. Exp. Med. (1992) v.175, 275-284.
(2) Mande S C et al., Science (1995) v.271, 203-207.