4PH8

Crystal structure of AggA, the major subunit of aggregative adherence fimbriae type I (AAF/I) from the Escherichia coli O4H104

Summary for 4PH8

• Entry DOI: 10.2210/pdb4ph8/pdb
• Related: 4OR1
• Descriptor: Aggregative adherence fimbrial subunit AggA, GLYCEROL (3 entities in total)
• Functional Keywords: cell adhesion, beta sandwich, donor-strand complementation, fibronectin binding
• Biological source: Escherichia coli O104:H4 str. C227-11
• Total number of polymer chains: 2
• Total formula weight: 33721.97

Authors

Pakharukova, N.A.,Tuitilla, M.,Zavialov, A.V. (deposition date: 2014-05-05, release date: 2014-10-01, Last modification date: 2024-10-23)

Primary citation

Berry, A.A.,Yang, Y.,Pakharukova, N.,Garnett, J.A.,Lee, W.C.,Cota, E.,Marchant, J.,Roy, S.,Tuittila, M.,Liu, B.,Inman, K.G.,Ruiz-Perez, F.,Mandomando, I.,Nataro, J.P.,Zavialov, A.V.,Matthews, S.
Structural Insight into Host Recognition by Aggregative Adherence Fimbriae of Enteroaggregative Escherichia coli.
Plos Pathog., 10:e1004404-e1004404, 2014

PubMed Abstract: Enteroaggregative Escherichia coli (EAEC) is a leading cause of acute and persistent diarrhea worldwide. A recently emerged Shiga-toxin-producing strain of EAEC resulted in significant mortality and morbidity due to progressive development of hemolytic-uremic syndrome. The attachment of EAEC to the human intestinal mucosa is mediated by aggregative adherence fimbria (AAF). Using X-ray crystallography and NMR structures, we present new atomic resolution insight into the structure of AAF variant I from the strain that caused the deadly outbreak in Germany in 2011, and AAF variant II from archetype strain 042, and propose a mechanism for AAF-mediated adhesion and biofilm formation. Our work shows that major subunits of AAF assemble into linear polymers by donor strand complementation where a single minor subunit is inserted at the tip of the polymer by accepting the donor strand from the terminal major subunit. Whereas the minor subunits of AAF have a distinct conserved structure, AAF major subunits display large structural differences, affecting the overall pilus architecture. These structures suggest a mechanism for AAF-mediated adhesion and biofilm formation. Binding experiments using wild type and mutant subunits (NMR and SPR) and bacteria (ELISA) revealed that despite the structural differences AAF recognize a common receptor, fibronectin, by employing clusters of basic residues at the junction between subunits in the pilus. We show that AAF-fibronectin attachment is based primarily on electrostatic interactions, a mechanism not reported previously for bacterial adhesion to biotic surfaces.

PubMed: 25232738
DOI: 10.1371/journal.ppat.1004404

Experimental method

X-RAY DIFFRACTION (1.55 Å)