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Salmonella Invasion Gene A (InvA)

A number of Gram-negative bacterial pathogens – including those causing disease in animals as well as plants - utilize a highly specialized nanomachine, termed the Type III Secretion System (T3SS), to achieve a remarkable translocation of bacterial proteins across three membranes and directly into the cytoplasm of the host organism.  These virulence proteins, often called "effectors," hijack eukaryotic biochemical processes in sophisticated ways for the benefit of the pathogen.  The secretion machinery itself appears to be highly conserved between different bacteria.

 

The engine of this complicated “molecular syringe” consists of a set of proteins in the inner membrane of these Gram-negative organisms, and extends into the cytoplasm, including an ATPase and several key transmembrane proteins.  InvA is a member of a set of several inner membrane proteins that form this core of the T3SS.  Highly conserved across pathogenic bacteria, as well as with a conserved homolog in the flagellar system (FlhA), InvA is critical to the functioning of the T3SS. However, the role of InvA, why it is important and how it functions in the T3SS, remains completely unknown. Outside of its sequence similarity to analogous components of other T3SSs, InvA shows no primary sequence similarity to any proteins of known function.

To begin to address some of these outstanding questions, we determined the crystal structure of a C-terminal fragment of InvA to 1.9 angstroms resolution.  This structure reveals the unexpected result that a set of structural domains that repeat in the proteins forming the basal body are also present in InvA, suggesting that large portions of the T3SS have been constructed from an evolutionarily conserved building block.

M. Lilic, C.M. Quezada, C.E. Stebbins. "A conserved domain in type III secretion links the cytoplasmic domain of InvA to elements of the basal body." (2010).  Acta Crystallogr D Biol Crystallogr. 2010 Jun;66(Pt 6):709-13. PMID: 20516623
[Abstract] [pdf] [pdb]

Dr. Mirjana Lilic was the lead scientist on the InvA project.