Two Proteins Form a Heteromeric Bacterial Self-Recognition Complex in Which Variable Subdomains Determine Allele-Restricted Binding

Self- versus nonself-recognition in bacteria has been described recently through genetic analyses in multiple systems; however, understanding of the biochemical properties and mechanisms of recognition-determinant proteins remains limited. Here we extend the molecular and biochemical understanding of two recognition-determinant proteins in bacteria. We have found that a heterotypic complex is formed between two bacterial self-recognition proteins, IdsD and IdsE, the genes of which have been shown to genetically encode the determinants for strain-specific identity in the opportunistic bacterial pathogen Proteus mirabilis. This IdsD-IdsE complex forms independently of other P. mirabilis-encoded self-recognition proteins. We have also shown that the binding between IdsD and IdsE is strain- and allele-specific. The specificity for interactions is encoded within a predicted membrane-spanning subdomain within each protein that contains stretches of unique amino acids in each P. mirabilis variant. Finally, we have demonstrated that this in vitro IdsD-IdsE binding interaction correlates to in vivo population identity, suggesting that the binding interactions between IdsD and IdsE are part of a cellular pathway that underpins self-recognition behavior in P. mirabilis and drives bacterial population sociality.