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Structure-function studies of organelle assembly and receptor recognition in organelles assembled via the chaperone/usher pathway

Berglund, Jenny (2004). Structure-function studies of organelle assembly and receptor recognition in organelles assembled via the chaperone/usher pathway. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae. Agraria, 1401-6249 ; 441
ISBN 91-576-6492-7
[Doctoral thesis]

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Adhesion is an important first step in infection, where the microorganism attaches to a host cell. In many cases adhesion is mediated by fimbriae, or pili; hairlike organelles composed of a large number of protein subunits, protruding out from the bacterial surface. In this thesis, the adhesion and assembly of two such organelles has been studied: type-1 pili from Escherichia coli and the capsular F1 antigen from Yersinia pestis. The adhesin molecule of type-1 pili is FimH, and the structure of the FimH lectin domain was determined to 2.3 Å. High structural similarity to the same domain in the FimH:FimC adhesin:chaperone structure shows rigidity and structural independency of the lectin domain. In the crystal structure a butyl mannoside was discovered in the FimH binding site. Binding studies of alkyl mannosides and aryl mannoside show that E. coli FimH recognizes these two classes of compounds with high affinity. Using a series of trimannosides corresponding to structures present in N-linked high-mannose glycoproteins, the binding properties of FimH from two different UPEC and one fecal E. coli strains were investigated. Our results suggest that the differences in adhesion phenotype mediated by these different adhesins are caused by differences in adhesin presentation rather than by affinity differences. The antiphagocytic capsule around Yersinia pestis is constructed from multiple copies of the Caf1 subunit assembled into thin fibres. The structure of the Caf1M:Caf1 chaperone:subunit binary complex and the Caf1M:Caf1:Caf1 ternary complex from Y. pestis was determined. Comparison of the chaperone bound Caf1 subunit with the Caf1 fibre subunit revealed that the Caf1M chaperone jams the folding of Caf1 in a high-energy conformation with a poorly packed hydrophobic core. When the chaperone dissociates and is replaced by the donor strand from the next subunit, folding is allowed to continue to completion. The folding energy released in this step is proposed to drive fibre assembly.

Authors/Creators:Berglund, Jenny
Title:Structure-function studies of organelle assembly and receptor recognition in organelles assembled via the chaperone/usher pathway
Series Name/Journal:Acta Universitatis Agriculturae Sueciae. Agraria
Year of publishing :March 2004
Number of Pages:56
ALLI. Zavialov, A., Berglund, J., and Knight, S. D. (2003a). Overexpression, purification, crystallization and preliminary X-ray diffraction analysis of the F1 antigen Caf1M-Caf1 chaperone-subunit pre-assembly complex from Yersinia pestis. Acta Crystallogr D Biol Crystallogr 59, 359-362. II. Zavialov, A. V., Berglund, J., Pudney, A. F., Fooks, L. J., Ibrahim, T. M., MacIntyre, S., and Knight, S. D. (2003b). Structure and biogenesis of the capsular F1 antigen from Yersinia pestis: preserved folding energy drives fiber formation. Cell 113, 587-596. III. Berglund, J., Schembri, M., Klemm, P., Zavialov, A., Choudhury, D., Oscarsson S., Knight, S.D. Structure and receptor binding properties of the FimH lectin domain from uropathogenic and fecal strains of Escherichia coli. In manuscript.
Place of Publication:Uppsala
ISBN for printed version:91-576-6492-7
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:X Agricola extesions > X30 Life sciences
Subjects:Not in use, please see Agris categories
Agrovoc terms:carbohydrates, lectins, urinary tract diseases, pathogenesis, immunoglobulins, vaccines
Keywords:carbohydrate binding, lectin, urinary tract infection, plague, antiphagocytic capsule, pathogenesis, donor strand complementation, donor strand exchange, immunoglobulin fold, vaccine, protein crystallography
Permanent URL:
ID Code:495
Department:(NL, NJ) > Dept. of Molecular Biology (until 131231)
Deposited By: Jenny Berglund
Deposited On:29 Mar 2004 00:00
Metadata Last Modified:02 Dec 2014 10:05

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