Assembly and architecture of the type III secretion sorting platform

Type III secretion systems are bacterial nanomachines specialized in protein delivery into target eukaryotic cells. The structural and functional complexity of these machines demands highly coordinated mechanisms for their assembly and operation. The sorting platform is a critical component of type III secretion machines that ensures the timely engagement and secretion of proteins destined to travel this export pathway. However, the mechanisms that lead to the assembly of this multicomponent structure have not been elucidated. Herein, employing an extensive in vivo cross-linking strategy aided by structure modeling, we provide a detailed intersubunit contact survey of the entire sorting platform complex. Using the identified cross-links as signatures for pairwise intersubunit interactions in combination with systematic genetic deletions, we mapped the assembly process of this unique bacterial structure. Insights generated by this study could serve as the bases for the rational development of antivirulence strategies to combat several medically important bacterial pathogens.

Automated summary

In this study, an extensive in vivo cross-linking strategy aided by structure modeling was used to investigate the sorting platform complex of type III secretion systems. The assembly process of this bacterial structure was mapped using identified cross-links as signatures for pairwise intersubunit interactions and systematic genetic deletions. Insights generated by this study could be used for the rational development of antivirulence strategies against medically important bacterial pathogens.