Structure of CfaA suggests a new family of chaperones essential for assembly of class 5 fimbriae.

Rui Bao,Di Xia,Yu-Xing Chen,Stephen J Savarino,April Fordyce,Annette Mcveigh,Andreas J Baumler

doi:10.1371/journal.ppat.1004316

Abstract

Adhesive pili on the surface of pathogenic bacteria comprise polymerized pilin subunits and are essential for initiation of infections. Pili assembled by the chaperone-usher pathway (CUP) require periplasmic chaperones that assist subunit folding, maintain their stability, and escort them to the site of bioassembly. Until now, CUP chaperones have been classified into two families, FGS and FGL, based on the short and long length of the subunit-interacting loops between its F1 and G1 β-strands, respectively. CfaA is the chaperone for assembly of colonization factor antigen I (CFA/I) pili of enterotoxigenic E. coli (ETEC), a cause of diarrhea in travelers and young children. Here, the crystal structure of CfaA along with sequence analyses reveals some unique structural and functional features, leading us to propose a separate family for CfaA and closely related chaperones. Phenotypic changes resulting from mutations in regions unique to this chaperone family provide insight into their function, consistent with involvement of these regions in interactions with cognate subunits and usher proteins during pilus assembly.

Highlights

Bacteria assemble filamentous projections on their surface to facilitate adhesion to other bacteria, eukaryotic cells and abiotic substrates
Each pilus protein subunit is assisted in folding by a chaperone that shuttles the subunit to an outer membrane usher complex, which serves as assembly platform
The colonization factor antigen I (CFA/I) pilus is the archetypal colonization factor (CF) for enterotoxigenic Escherichia coli, a major cause of life-threatening, dehydrating diarrhea in young children of low-income countries and in travelers to these regions. This structure reveals unique features that allow us to define a new class of chaperones that assist pilus assembly in bacteria

Summary

Introduction

Bacteria assemble filamentous projections on their surface to facilitate adhesion to other bacteria, eukaryotic cells and abiotic substrates. The chaperone-pilin complex docks with the outer membrane usher and inserts a supernumerary Nterminal pilin b-strand into the hydrophobic groove of a foregoing pilin, thereby displacing the chaperone G1 strand from the latter by a ‘zip-in, zip-out’ process called donor strand exchange (DSE) [5]. Ordered iterations of this cycle drive pilus elongation and extrusion from the bacterial surface through the usher pore

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