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

Ben R Otto,Robert Sijbrandi,Joen Luirink,Bauke Oudega,Jonathan G Heddle,Kenji Mizutani,Sam-Yong Park,Jeremy R.H Tame

doi:10.1074/jbc.m412885200

Ben R Otto, Robert Sijbrandi + Show 6 more

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https://doi.org/10.1074/jbc.m412885200

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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 beta-helical structure yet solved.

Highlights

The acquisition of iron is essential for the survival of pathogenic bacteria, which have 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
Hbp was first purified from E. coli EB1, a strain isolated from an intra-abdominal wound infection [22]

Summary

Introduction

The acquisition of iron is essential for the survival of pathogenic bacteria, which have evolved a wide variety of uptake systems to extract iron and heme from host proteins such as hemoglobin. AT passenger domains are generally more than 100 kDa in size and vary widely in sequence and function but include a group of closely related serine proteases, the SPATE family (serine protease autotransporters of the Enterobacteriaceae) These proteins are found only in pathogenic bacteria, but their precise roles remain unknown [8, 9]. We have determined the crystal structure of Hbp with the longer term view of producing inhibitors, vaccines, or other treatments for peritonitis and other diseases caused by SPATE proteins. From this first molecular model of an AT, we have

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