The structural homology between uteroglobin and the pore-forming domain of colicin A suggests a possible mechanism of action for uteroglobin.

Although the exact physiological function of uteroglobin is not known, it has been suggested that it may function by inhibiting phospholipase A2. We have found that the uteroglobin fold is embedded in that of the poreforming domain of colicin A. Colicin A is an antibiotic protein that kills sensitive Escherichia coli cells by forming a pore in their phospholipid membrane. The RMS deviation between the C alpha atoms after the structural alignment is 2.39 A for the 52 superimposed residues. In the alignment, uteroglobin helices 1, 2, 3, and 4 align with colicin A helices 6, 7, 3, and 4, respectively. The motif is strongly amphipathic in both proteins. On the basis of this common structural motif and of known experimental data on both proteins, we propose that UG binds to the membrane surface by lying on it monotopically. The phospholipase A2 inhibition would follow this initial binding step.