title: A small conserved motif supports polarity augmentation of Shigella flexneri IcsA.
abstract: The rod-shaped enteric intracellular pathogen Shigella flexneri and other Shigella species are the causative agents of bacillary dysentery. S. flexneri are able to spread within the epithelial lining of the gut, resulting in lesion formation, cramps and bloody stools. The outer membrane protein IcsA is essential for this spreading process. IcsA is the initiator of an actin-based form of motility whereby it allows the formation of a filamentous actin 'tail' at the bacterial pole. Importantly, IcsA is specifically positioned at the bacterial pole such that this process occurs asymmetrically. The mechanism of IcsA polarity is not completely understood, but it appears to be a multifactorial process involving factors intrinsic to IcsA and other regulating factors. In this study, we further investigated IcsA polarization by its intramolecular N-terminal and central polar-targeting (PT) regions (nPT and cPT regions, respectively). The results obtained support a role in polar localization for the cPT region and contend the role of the nPT region. We identified single IcsA residues that have measurable impacts on IcsA polarity augmentation, resulting in decreased S. flexneri sprading efficiency. Intriguingly, regions and residues involved in PT clustered around a highly conserved motif which may provide a functional scaffold for polarity-augmenting residues. How these results fit with the current model of IcsA polarity determination is discussed.
authors: 1​Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia.
authors: Matthew Thomas
authors: MT
authors: Doyle
authors: 2​Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
authors: Marcin
authors: M
authors: Grabowicz
authors: 1​Department of Molecular and Cellular Biology, School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia.
authors: Renato
authors: R
authors: Morona
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D021381:Protein Transport; D012763:Shigella flexneri / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C058483:virG protein, Shigella flexneri