1.C.113.  The Hemolysin III (Hly III) Family

The Hly III family (SwissProt family UPF0073) consists of proteins of 200-250 residues with 7 putative TMSs. They are from bacteria and eukaryotes (both plants and animals). One is a characterized hemolysin from Bacillus cereus. Another is a protein induced during differentiation of monocytes to macrophage in humans.

Bacillus cereus hemolysin III activity has been tested in crude extracts, and from Escherichia coli carrying the hly-III gene (Baida and Kuzmin 1996). It was concluded that hemolysin III is a pore-forming hemolysin with functional pore diameter of about 3-3.5 nm. Hemolysis occurs in at least three steps: (i) the temperature-dependent binding of the Hly-III monomers to the erythrocyte membrane; (ii) the temperature-dependent formation of the transmembrane oligomeric pore, and (iii) the temperature-independent erythrocyte lysis.

One homologue is a receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism (Tanabe et al. 2015, Yamauchi et al. 2003). Required for normal glucose and fat homeostasis and for maintaining normal body weight. ADIPOQ-binding activates a signaling cascade that leads to increased AMPK activity, and ultimately to increased fatty acid oxidation, increased glucose uptake and decreased gluconeogenesis. This receptor has high affinity for globular adiponectin and low affinity for full-length adiponectin.  The relationship between this receptor and the hemolysins is not clear, but they are definitely homologous with the same general topology.