title: Dimerisation and structural integrity of Heparin Binding Hemagglutinin A from Mycobacterium tuberculosis: implications for bacterial agglutination.
abstract: Heparin Binding Hemagglutinin A (HBHA) is hitherto the sole virulence factor associated with tuberculosis dissemination from the lungs, the site of primary infection, to epithelial cells. We have previously reported the solution structure of HBHA, a dimeric and elongated molecule. Since oligomerisation of HBHA is associated with its ability to induce bacterial agglutination, we investigated this process using experimental and modelling techniques. We here identified a short segment of HBHA whose presence is mandatory for the stability of folded conformation, whose denaturation is a reversible two-state process. Our data suggest that agglutination-driven cell-cell interactions do not occur via association of HBHA monomers, nor via association of HBHA dimers and open the scenario to a possible trans-dimerisation process.
authors.affiliation: Istitute of Biostructures and Bioimaging, CNR, Naples, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Esposito
authors.forename: Paola
authors.initials: P
authors.lastname: Carullo
authors.forename: Emilia
authors.initials: E
authors.lastname: Pedone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Graziano
authors.forename: Pompea
authors.initials: P
authors.lastname: Del Vecchio
authors.forename: Rita
authors.initials: R
authors.lastname: Berisio
mesh_terms: D000371:Agglutination; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism; D001422:Bacterial Adhesion / Q000502:physiology; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D008027:Light; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000378:metabolism* / Q000502:physiology; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization; D055550:Protein Stability; D012542:Scattering, Radiation; D013696:Temperature
chemical_list: D000942:Antigens, Bacterial; D037102:Lectins; C104578:heparin-binding hemagglutinin; C072681:Mycobacterium tuberculosis antigens