Physical Sciences and Mathematics Commons^™

Interfacial Amino Acids Support Spa47 Oligomerization And Shigella Type Three Secretion System Activation, Hannah J. Demler, Heather B. Case, Yalemi Morales, Abram R. Bernard, Sean J. Johnson, Nicholas E. Dickenson

Chemistry and Biochemistry Faculty Publications

Like many Gram-negative pathogens, Shigella rely on a type three secretion system (T3SS) for injection of effector proteins directly into eukaryotic host cells to initiate and sustain infection. Protein secretion through the needle-like type three secretion apparatus (T3SA) requires ATP hydrolysis by the T3SS ATPase Spa47, making it a likely target for in vivo regulation of T3SS activity and an attractive target for small molecule therapeutics against shigellosis. Here, we developed a model of an activated Spa47 homo-hexamer, identifying two distinct regions at each protomer interface that we hypothesized to provide intermolecular interactions supportingSpa47 oligomerization and enzymatic activation. Mutational analysis …