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 phospholipas e A(2). We have found that the uteroglobin fold is embedded in that of the pore-forming domain of colicin A. Colicin A is an antibiotic prot ein that kills sensitive Escherichia coli cells by forming a pore in t heir phospholipid membrane. The RMS deviation between the C-alpha atom s after the structural alignment is 2.39 Angstrom for the 52 superimpo sed residues. In the alignment, uteroglobin helices 1, 2, 3, and 4 ali gn with colicin A helices 6, 7, 3, and 4, respectively. The motif is s trongly amphipathic in both proteins. On the basis of this common stru ctural motif and of known experimental data on both proteins, we propo se that UG binds to the membrane surface by lying on it monotopically. The phospholipase A(2) inhibition would follow this initial binding s tep.