Second truncated hemoglobin as O2 and not NO transporter in Mycobacterium Tuberculosis

MATIAS VILLARRUEL; DAIANA CAPDEVILA; MAURO BRINGAS

Congreso; American Gasotransmitter Symposium 2020; 2020

Mycobacterium tuberculosis, an obligated aerobe, can survive the host´s innate immune response and enter a latency state by forming multicellular structures called granulomas. Inside these structures the pathogen is still able to proliferate even though it is exposed to high nitrosative stress and low oxygen concentrations. A pair of truncated hemoglobin has been found in Mt, HbN and HbO. Previous work proposed HbN as the responsible of biding to and degrading NO. The high affinity for oxygen and low for NO of HbO makes its role unclear. We propose that HbO has its oxygen biding affinity allosterically modified by the interaction with the pathogen membranes and aids in the survival of Mt during latency by allowing oxygen transfer to the membrane.We have performed coarse grain molecular dynamics simulations to assess the interaction between HbO and membranes and begin to explore its molecular basis by analyzing the preferred protein orientation at the time of contact with the membrane after a free trajectory starting in random conformations. In future work, we aim to measure quantitatively the binding affinity between HbO bound to different Fe axial ligands (CO, H2O) with biomimetic liposomes with ITC experiments. The resulting allosteric coupling will test the effect of the membranes in the affinity with ligands.