The Tip Complex: From Host Cell Sensing to Translocon Formation

Type III secretion systems are used by some Gram-negative bacteria to inject effector proteins into targeted eukaryotic cells for the benefit of the bacterium. The type III secretion injectisome is a complex nanomachine comprised of four main substructure

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Introduction.......................................................................................................................... The Type III Secretion Apparatus or Injectisome (The Injectisome) ................................ The Injectisome Needle Tip Complex ................................................................................ 3.1 Discovery of the Nascent Tip Complex Protein and Overall Structure.................... 3.2 Maturation of the Tip Complex in Shigella .............................................................. 3.3 The Translocon ........................................................................................................... 3.4 Where Does the Tip Complex End and the Translocon Begin ................................ 4 Sensing the Signals Responsible for Type III Secretion Induction in Shigella................. 4.1 Invasion Plasmid Antigen D ...................................................................................... 4.2 Invasion Plasmid Antigen B ...................................................................................... 5 Concluding Remarks ........................................................................................................... References ..................................................................................................................................

Abstract Type III secretion systems are used by some Gram-negative bacteria to inject effector proteins into targeted eukaryotic cells for the benefit of the bacterium. The type III secretion injectisome is a complex nanomachine comprised of four main substructures including a cytoplasmic sorting platform, an envelope-spanning basal body, an extracellular needle and an exposed needle tip complex. Upon contact with a host cell, secretion is induced, resulting in the formation of a translocon pore in the host membrane. Translocon formation completes the conduit needed for effector secretion into the host cell. Control of type III secretion occurs in response to environmental signals, with the final signal being host cell contact. Secretion control W. D. Picking (&) Department of Pharmaceutical Chemistry, University of Kansas, 2030 Becker Drive, Lawrence 66047, KS, USA e-mail: [email protected] M. L. Barta Higuchi Biosciences, 2099 Constant Ave., Lawrence 66047, KS, USA Present Address: M. L. Barta Catalent Pharma Solutions, 10245 Hickman Mills Drive, Kansas City 64137, MO, USA Current Topics in Microbiology and Immunology https://doi.org/10.1007/82_2019_171 © Springer Nature Switzerland AG 2019

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W. D. Picking and M. L. Barta

occurs primarily at two sites—the cytoplasmic sorting platform, which determines secretion hierarchy, and the needle tip complex, which is critical for sensing and responding to environmental signals. The best-characterized injectisomes are those from Yersinia, Shigella and Salmonella species where there is a wealth of information on the tip complex and the two translocator proteins. Of these systems, the best characterized from a se