It seems that a heme molecule itself can regulate many physiological processes in many organisms including humans. The role of the heme in such a regulation is mediated by a group of hemoproteins called heme-containing sensor proteins. Generally, it is known that the heme can act as (A) a preliminary signal of heme sensor proteins and (B) a gas sensing site of heme-based gas sensor proteins.

Initially, I studied a “heme-regulated eukaryotic initiation factor 2α (eIF2α) kinase” or “heme-regulated inhibitor” (HRI), a protein from the group (A). Once I established my own group I turned my attention to the proteins from the (B) category. Namely, a “globin-coupled histidine kinase“ (AfGcHK) from Anaeromyxobacter sp. strain Fw109-5, a “globin-coupled heme-based oxygen sensor diguanylate cyclase“ from Escherichia coli (YddV) and a “direct oxygen sensor” from Escherichia coli (EcDOS) showing the phosphodiesterase activity. Our research contributes to expand our understanding of heme-containing sensor proteins‘ function. Although the proteins are involved in various important physiological functions, the molecular mechanism of their sensing functions and signal transduction remains still to be elucidated. Especially the interaction between two domains, the heme-containing sensor and its functional domains, is currently studied by various techniques (spectroscopy, hydrogen-deuterium exchange, enzyme kinetic analysis, crystallography etc.). Moreover, our work sheds more light on protein-protein and inter domain interaction in general.

The project has unquestionable practical importance. For example implication of HRI in process of human lung carcinogenesis and YddV in pathogenic bacteria biofilm formation makes the heme-containing sensor proteins unique target for our studies in order to be able to control such processes. Moreover, it is reasonable to suggest that many crucial functions associated with heme, in both health and disease, remain to be discovered in near future.

Mechanism of action of heme sensor proteins (A) and heme-based gas sensor proteins (B).

If you want to know more details about heme-containing proteins, you can see the record of the lecture from the Biochemistry meeting in 2016 here. (The introduction of the lecture is in Czech language, but the lecture is than presented in English).