Contact person: Rita Berisio, rita.berisio
unina.itActors: EmiliaMaria Pedone, emilia.pedone
cnr.it, Rita Berisio, rita.berisiounina.it, Tuberculosis is one of the main causes of infectious disease mortality in the world. The interaction between M. tuberculosis (MTB) and the human host after infection, often starting in the lungs, may manifest itself as a chronic disease or as a latent (or dormant) infection, a state capable to evade host responses. The probability of reactivation from dormancy is strongly affected by the type of host immune response and it is significantly enhanced in immuno-compromised patients. We have determined the first crystal structures of a Resuscitation Promoting Factors. These studies have provided insights into the mechanism of bacterial revival. M. tuberculosis is also able to invade and replicate within extra-pulmonary cell types, like epithelial cells. Adherence of the tubercle bacillus to epithelial cells is mediated by the heparin-binding hemagglutinin adhesin (HBHA), a 199-residue surface-exposed protein. The adherence of the bacterium mediated by HBHA relies on the interaction of its C-terminus (composed of lysine-rich motifs) with heparan sulfate-containing proteoglycans on the surface of epithelial cells. HBHA is also responsible for bacterial hemagglutination, a process which is essential to MTB infection. A thorough biochemical characterisation of HBHA has provided experimental evidence of a coiled coil nature of HBHA. These data, together with the low resolution structure of both a full-length and a truncated form of HBHA by Small Angle X-ray Scattering have unambiguously indicated that HBHA has a dimeric structure with an elongated shape. Our data provide insights into the twofold role of HBHA both for adhesion of M. tuberculosis to host epithelial cells and as an agglutination factor
1. Calvanese, L., Falcigno, L., Maglione, C., Marasco, D., Ruggiero, A., Squeglia, F., Berisio, R. & D'Auria, G. (2013). Structural and binding properties of the PASTA domain of PonA2, a key penicillin binding protein from Mycobacterium tuberculosis. Biopolymers. In the press.
2. Cantisani, M., Falanga, A., Incoronato, N., Russo, L., De Simone, A., Morelli, G., Berisio, R., Galdiero, M. & Galdiero, S. (2013). Conformational Modifications of gB from Herpes Simplex Virus Type 1 Analyzed by Synthetic Peptides. Journal of medicinal chemistry.
8. Berisio, R. & Vitagliano, L. (2012). Polyproline and triple helix motifs in host-pathogen recognition. Current protein & peptide science 13, 855-65.
9. Ruggiero, A., De Simone, P., Smaldone, G., Squeglia, F. & Berisio, R. (2012). Bacterial cell division regulation by Ser/Thr kinases: a structural perspective. Current protein & peptide science 13, 756-66.
12. Berisio, R. (2012). Editorial: cell processes in bacterial diseases. Protein and peptide letters 19, 1011-2.
13. Di Maro, A., Berisio, R., Ruggiero, A., Tamburino, R., Severino, V., Zacchia, E. & Parente, A. (2012). Structural and enzymatic properties of an in vivo proteolytic form of PD-S2, type 1 ribosome-inactivating protein from seeds of Phytolacca dioica L. Biochemical and biophysical research communications 421, 514-20.
4. Ruggiero, A., Smaldone, G., Squeglia, F. & Berisio, R. (2012). Enhanced crystallizability by protein engineering approaches: a general overview. Protein and peptide letters 19, 732-42.
15. Esposito, C., Cantisani, M., D'Auria, G., Falcigno, L., Pedone, E., Galdiero, S. & Berisio, R. (2012). Mapping key interactions in the dimerization process of HBHA from Mycobacterium tuberculosis, insights into bacterial agglutination. FEBS letters 586, 659-67.
16. Squeglia, F., Marchetti, R., Ruggiero, A., Lanzetta, R., Marasco, D., Dworkin, J., Petoukhov, M., Molinaro, A., Berisio, R. & Silipo, A. (2011). Chemical basis of peptidoglycan discrimination by PrkC, a key kinase involved in bacterial resuscitation from dormancy. Journal of the American Chemical Society 133, 20676-9.
17. Ruggiero, A., Dattelbaum, J. D., Pennacchio, A., Iozzino, L., Staiano, M., Luchansky, M. S., Der, B. S., Berisio, R., D'Auria, S. & Vitagliano, L. (2011). Crystallization and preliminary X-ray crystallographic analysis of ligand-free and arginine-bound forms of Thermotoga maritima arginine-binding protein. Acta crystallographica. Section F, Structural biology and crystallization communications 67, 1462-5.
19. Vitagliano, L., Berisio, R. & De Simone, A. (2011). Role of hydration in collagen recognition by bacterial adhesins. Biophysical journal 100, 2253-61.
20. Ruggiero, A., Squeglia, F., Marasco, D., Marchetti, R., Molinaro, A. & Berisio, R. (2011). X-ray structural studies of the entire extracellular region of the serine/threonine kinase PrkC from Staphylococcus aureus. The Biochemical journal 435, 33-41.
21. Ruggiero, A., Squeglia, F., Pirone, L., Correale, S. & Berisio, R. (2011). Expression, purification, crystallization and preliminary X-ray crystallographic analysis of a major fragment of the resuscitation-promoting factor RpfB from Mycobacterium tuberculosis. Acta crystallographica. Section F, Structural biology and crystallization communications 67, 164-8.
24. Ruggiero, A., Squeglia, F., Izzo, V., Silipo, A., Vitagliano, L., Molinaro, A. & Berisio, R. (2010). Expression, purification, crystallization and preliminary X-ray crystallographic analysis of the peptidoglycan binding region of the Ser/Thr kinase PrkC from Staphylococcus aureus. Protein and peptide letters 17, 1296-9.
25. Esposito, C., Carullo, P., Pedone, E., Graziano, G., Del Vecchio, P. & Berisio, R. (2010). Dimerisation and structural integrity of Heparin Binding Hemagglutinin A from Mycobacterium tuberculosis: implications for bacterial agglutination. FEBS letters 584, 1091-6.
26. Severino, V., Chambery, A., Di Maro, A., Marasco, D., Ruggiero, A., Berisio, R., Giansanti, F., Ippoliti, R. & Parente, A. (2010). The role of the glycan moiety on the structure-function relationships of PD-L1, type 1 ribosome-inactivating protein from P. dioica leaves. Molecular bioSystems 6, 570-9.
27. Ruggiero, A., Squeglia, F., Esposito, C., Marasco, D., Pedone, E., Pedone, C. & Berisio, R. (2010). Expression, purification, crystallization and preliminary X-ray crystallographic analysis of the resuscitation promoting factor interacting protein RipA from M. tuberculosis. Protein and peptide letters 17, 70-3.
31. Berisio, R., De Simone, A., Ruggiero, A., Improta, R. &
Vitagliano, L. (2009). Role of side chains in collagen triple helix stabilization and partner
recognition. Journal of peptide science :
an official publication of the European Peptide Society 15, 131-40.
32. Vitagliano, L., Ruggiero, A., Pedone, C. & Berisio, R.
(2009). Molecular dynamics
studies of the P pilus rod subunit PapA. Journal
of peptide science : an official publication of the European Peptide Society
15, 192-9.
33. Ruggiero, A., Tizzano, B., Pedone, E.,
Pedone, C., Wilmanns, M. & Berisio, R. (2009). Crystal structure of the
resuscitation-promoting factor (DeltaDUF)RpfB from M. tuberculosis. Journal of molecular biology 385, 153-62.
Search related bibliography on PubMed
1074 views. Last view on Saturday 12 October 2024, 17:59:08
ibb.cnr.it
