title: An arm-swapped dimer of the Streptococcus pyogenes pilin specific assembly factor SipA.
abstract: Streptococcus pyogenes (group A streptococcus [GAS]) is a major human pathogen. Attachment of GAS to host cells depends in large part on pili. These assemblies are built from multiple covalently linked subunits of a backbone protein (FctA), which forms the shaft of the pilus, and two minor pilin proteins, FctB anchoring the pilus to the cell wall and Cpa functioning as the adhesin at the tip. Polymerisation of the pilin subunits is mediated by a specific sortase, which catalyzes the formation of peptide bonds linking successive subunits. An additional gene, SipA, is also essential for GAS pilus polymerisation, but its function remains undefined. Here we report the crystal structure of a truncated SipA protein from GAS, determined at 1.67Å resolution. The structure reveals that SipA has the same core fold as the Escherichia coli type-I signal peptidase (SPase-I), but has a much smaller non-catalytic domain. The truncated protein, which lacks 9 N-terminal residues, forms an arm-swapped dimer in which the C-terminal β-strand of each monomer crosses over to interact with an N-terminal strand from the other monomer. In addition, there is no peptide binding cleft and significant differences in the putative membrane association region.
authors.affiliation: School of Biological Sciences, University of Auckland, Auckland, New Zealand. p.young@auckland.ac.nz
authors.forename: Paul G
authors.initials: PG
authors.lastname: Young
authors.forename: Hae Joo
authors.initials: HJ
authors.lastname: Kang
authors.forename: Edward N
authors.initials: EN
authors.lastname: Baker
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D003001:Cloning, Molecular; D019281:Dimerization; D010861:Fimbriae, Bacterial / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013297:Streptococcus pyogenes / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D001426:Bacterial Proteins
keywords: LepA; Pilus assembly; Signal peptidase; SipA; Streptococcus pyogenes