title: The structure of the CS1 pilus of enterotoxigenic Escherichia coli reveals structural polymorphism.
abstract: Enterotoxigenic Escherichia coli (ETEC) is a bacterial pathogen that causes diarrhea in children and travelers in developing countries. ETEC adheres to host epithelial cells in the small intestine via a variety of different pili. The CS1 pilus is a prototype for a family of related pili, including the CFA/I pili, present on ETEC and other Gram-negative bacterial pathogens. These pili are assembled by an outer membrane usher protein that catalyzes subunit polymerization via donor strand complementation, in which the N terminus of each incoming pilin subunit fits into a hydrophobic groove in the terminal subunit, completing a β-sheet in the Ig fold. Here we determined a crystal structure of the CS1 major pilin subunit, CooA, to a 1.6-Å resolution. CooA is a globular protein with an Ig fold and is similar in structure to the CFA/I major pilin CfaB. We determined three distinct negative-stain electron microscopic reconstructions of the CS1 pilus and generated pseudoatomic-resolution pilus structures using the CooA crystal structure. CS1 pili adopt multiple structural states with differences in subunit orientations and packing. We propose that the structural perturbations are accommodated by flexibility in the N-terminal donor strand of CooA and by plasticity in interactions between exposed flexible loops on adjacent subunits. Our results suggest that CS1 and other pili of this class are extensible filaments that can be stretched in response to mechanical stress encountered during colonization.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia Medical Center, Charlottesville, VA, USA. galkin@virginia.edu
authors.forename: Vitold E
authors.initials: VE
authors.lastname: Galkin
authors.forename: Subramaniapillai
authors.initials: S
authors.lastname: Kolappan
authors.forename: Dixon
authors.initials: D
authors.lastname: Ng
authors.forename: ZuSheng
authors.initials: Z
authors.lastname: Zong
authors.forename: Juliana
authors.initials: J
authors.lastname: Li
authors.forename: Xiong
authors.initials: X
authors.lastname: Yu
authors.forename: Edward H
authors.initials: EH
authors.lastname: Egelman
authors.forename: Lisa
authors.initials: L
authors.lastname: Craig
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D054307:Enterotoxigenic Escherichia coli / Q000737:chemistry* / Q000648:ultrastructure*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D036781:Fimbriae Proteins / Q000737:chemistry*; D010861:Fimbriae, Bacterial / Q000737:chemistry* / Q000648:ultrastructure*; D008854:Microscopy, Electron; D008958:Models, Molecular; D008969:Molecular Sequence Data
chemical_list: C088904:CooA protein, E coli; D029968:Escherichia coli Proteins; D036781:Fimbriae Proteins