Dimerisation and structural integrity of Heparin Binding Hemagglutinin A from Mycobacterium tuberculosis: Implications for bacterial agglutination

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.

Structured summary

MINT-7709940, MINT-7709948: HBHA (uniprotkb:A5TZK3) and HBHA (uniprotkb:A5TZK3) bind (MI:0407) by circular dichroism (MI:0016)MINT-7709966: HBHA (uniprotkb:A5TZK3) and HBHA (uniprotkb:A5TZK3) bind (MI:0407) by biophysical (MI:0013)MINT-7709955: HBHA (uniprotkb:A5TZK3) and HBHA (uniprotkb:A5TZK3) bind (MI:0407) by dynamic light scattering (MI:0038)