UC San Diego

The SdpI family consists of putative bacterial toxin immunity and signal transduction proteins. One member of the family in Bacillus subtilis, SdpI, provides immunity to cells from cannibalism in times of nutrient limitation. SdpI family members are transmembrane proteins with 3, 4, 5, 6, 7, 8 or 12 putative transmembrane [alpha]-helical segments (TMSs). These varied topologies appear to be genuine rather than artifactual due to sequencing or annotation errors. Bioinformatic methods were used to show that the basic and most frequently occurring element of the SdpI family has 6 TMSs. Homologues of all topological types were aligned to determine the homologous TMSs and loop regions, and the Positive-Inside Rule was used to determine sidedness. The two most conserved motifs were identified between TMSs 1 and 2 and TMSs 4 and 5 of the 6 TMS proteins. These showed significant sequence similarity, leading us to suggest that the primordial precursor of these proteins was a 3 TMS-encoding genetic element that underwent intragenic duplication. Various fusional, insertional and deletion events, as well as intragenic duplications and inversions, are proposed to have yielded SdpI homologues with topologies of varying numbers of TMSs. We propose a specific evolutionary pathway that could have given rise to these distantly related bacterial immunity proteins. Our analyses allow us to propose structure-function relationships that may be applicable to most or all family members