Mapping key interactions in the dimerization process of HBHA from Mycobacterium tuberculosis, insights into bacterial agglutination.
HBHA is a cell-surface protein implicated in the dissemination of Mycobacterium tuberculosis (Mtb) from the site of primary infection. Its N-terminal coiled-coil region is also involved in bacterial agglutination. However, despite the importance of HBHA dimerization in agglutination, protein regions involved in dimerization are hitherto not known. Here, we mapped these regions by coupling peptide synthesis, biochemical and computational analyses, and identified structural determinants for HBHA monomer-monomer recognition. Importantly, we obtained the first molecule able to induce HBHA dimer disaggregation at 37°C, the typical growth temperature of Mtb. This result provides new opportunities towards the development of Mtb anti-aggregation molecules with therapeutic interest.
Institute of Biostructures and Bioimaging, CNR, Napoli, Italy.
Carla
C
Esposito
Marco
M
Cantisani
Gabriella
G
D'Auria
Lucia
L
Falcigno
Emilia
E
Pedone
Stefania
S
Galdiero
Rita
R
Berisio
D000371:Agglutination / Q000502:physiology*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D013696:Temperature
D001426:Bacterial Proteins; C440647:HbhA protein, Mycobacterium tuberculosis; D008565:Membrane Proteins; D010455:Peptides