title: Triggered Mycobacterium tuberculosis heparin-binding hemagglutinin adhesin folding and dimerization.
abstract: The heparin-binding hemagglutinin adhesin (HBHA) is a surface adhesin on the human pathogen Mycobacterium tuberculosis. Previously, it has been shown that HBHA exists as a dimer in solution. We investigated the detailed nature of this dimer using circular dichroism spectroscopy and analytical ultracentrifugation techniques. We demonstrate that the heparan sulfate (HS) binding region does not play a role in dimerization in solution, while the linker region between the predicted N-terminal coiled-coil and the C-terminal HS binding region does affect dimer stability. The majority of contacts responsible for dimerization, folding, and stability lie within the predicted coiled-coil region of HBHA, while the N-terminal helix preceding the coiled-coil appears to trigger the folding and dimerization of HBHA. Constructs lacking this initial helix or containing site-specific mutations produce nonhelical monomers in solution. Thus, we show that HBHA dimerization and folding are linked and that the N-terminal region of this cell surface adhesin triggers the formation of an HBHA coiled-coil dimer.
authors.affiliation: University of North Carolina-Chapel Hill, Dept. of Chemistry, Chapel Hill, NC 27599-3290, USA.
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Lomino
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Tripathy
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Redinbo
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D001426:Bacterial Proteins; C440647:HbhA protein, Mycobacterium tuberculosis; D008565:Membrane Proteins