Periscope Proteins are variable-length regulators of bacterial cell surface interactions

Changes at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal Periscope Proteins as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus, variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly available long read genome sequencing data, we propose that this class could contain over 50 distinct proteins, including those implicated in host colonization and biofilm formation by human pathogens. In large multidomain proteins, sequence divergence between adjacent domains appears to reduce interdomain misfolding. Periscope Proteins break this rule, suggesting that their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria, and the immune system.

Automated summary

Changes at the cell surface enable bacteria to survive in dynamic environments, with Periscope Proteins identified as a common mechanism for bacterial surface alteration through protein length variation. These proteins, forming elongated rod-like structures, can have over 50 distinct variants implicated in host colonization and biofilm formation. While sequence divergence in large multidomain proteins may reduce misfolding between domains, Periscope Proteins break this rule and suggest that their length variability is crucial in regulating bacterial interactions with host surfaces and the immune system.