Crystal Structure of Hemoglobin Protease, a Heme Binding Autotransporter Protein from Pathogenic Escherichia coli

Abstract

The acquisition of iron is essential for the survival of pathogenic bacteria, which have consequently evolved a wide variety of uptake systems to extract iron and heme from host proteins such as hemoglobin. Hemoglobin protease (Hbp) was discovered as a factor involved in the symbiosis of pathogenic Escherichia coli and Bacteroides fragilis, which cause intra-abdominal abscesses.Released from E. coli, this serine protease autotransporter degrades hemoglobin and delivers heme to both bacterial species. The crystal structure of the complete passenger domain of Hbp (110 kDa) is presented, which is the first structure from this class of serine proteases and the largest parallel ␤-helical structure yet solved.

Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain

“…5). This packing is consistent with the elution of p55 as a dimer from gel filtration columns (see Methods) and a previous EM study indicating that a p55 domain secreted by H. pylori formed dimers (29 (42), and VacA p55 do not share sequence similarities, but all contain a ␤-helix fold. The ␤-helix fold is composed of multiple Ϸ25-aa quasirepeats, each of which forms a single coil of the helix.…”

The antigen 43 structure reveals a molecular Velcro-like mechanism of autotransporter-mediated bacterial clumping

“…Despite their abundance and the increasing amount of data linking AT proteins to bacterial virulence, very little structural information is available at a molecular level for these proteins. In fact, AT proteins are significantly underrepresented in the Protein Data Bank (PDB), with only 1 fulllength AT structure, 7 AT passenger domains, 5 AT β-domains, and 12 small domains of trimeric autotransporters deposited among the ∼87,500 structures currently available in the PDB (9,18,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). None of these entries belong to the large family of AIDA-I-type AT proteins from Gamma-Proteobacteria (3,16).…”

A conserved stable core structure in the passenger domain β‐helix of autotransporter virulence proteins

“…5 The crystal structure of the porin domain from the AT NalP revealed a pore diameter that is too small (1-2 nm) to allow passage of a folded passenger domain, suggesting the passenger domain might pass through the porin unfolded, then fold extracellularly. 6 The crystal structures of two AT passenger domains have been solved: pertactin 7 and hemoglobin protease 8 (Figure 1), as well as a portion of the VacA passenger domain. 9 All three structures include a long right-handed parallel b-helical structure, and pertactin and Hbp are the two longest b-helical structures solved to date.…”