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SUMMARY:Structure of a Chaperone-Usher pilus reveals the molecular basis o
 f rod uncoiling
DTSTART:20170718T121500
DTSTAMP:20260505T122154Z
UID:1d5e7679dbf7017b9e5a13584f2e8c9f1cd0b5d8539eabf6d715e7c9
CATEGORIES:Conferences - Seminars
DESCRIPTION:Manuela Hospenthal\, Institute of Structural and Molecular Bio
 logy\, Department of Biological Sciences\, Birkbeck College\, University o
 f London\nChaperone-usher (CU) pili are ubiquitously displayed appendages 
 on the surface of bacterial pathogens. These remarkable protein structures
  are crucial virulence factors that allow bacteria to attach and spread wi
 thin the urinary tract. Type 1 and P pili are the most abundant CU pili pr
 oduced by uropathogenic Escherichia coli (UPEC)\, which are responsible fo
 r ~80% of all urinary tract infections (UTIs). Due to their prevalence\, U
 TIs contribute significantly to antibiotic use and the emergence of resist
 ance.  CU pili are organised into two subassemblies: the tip fibrillum an
 d a 1-2 µm long rod\, which is in turn composed of ~1000 copies of a sing
 le subunit.\n\nHere\, we present an atomic model of the P pilus rod genera
 ted from a 3.8 Å resolution cryo-electron microscopy reconstruction. The 
 rod adopts a superhelical quaternary structure\, which endows it with rema
 rkable spring-like properties\, allowing pili to reversibly uncoil when su
 bjected to flow-induced shear forces in the urinary tract. Strikingly\, ea
 ch pilus subunit contacts ten other subunits forming an extensive interact
 ion network\, revealing the molecular basis for the rod’s mechanical pro
 perties. By targeting key residues in this interaction network by mutagene
 sis\, we identified important sites of the pilus subunit essential for the
  integrity of the quaternary pilus rod structure\, since mutation led to a
 brogation of rod polymerization in vitro.\n\nIn summary\, this structure r
 eveals the molecular basis for pilus rod uncoiling\, a key adaptation of C
 U pili and the bacterial pathogens that display them. Moreover\, it will a
 llow us to address unanswered questions about CU pilus biogenesis in the f
 uture. Ultimately\, detailed knowledge of the pilus rod structure\, in con
 junction with an understanding of its functional role in pilus translocati
 on\, will provide a unique opportunity to develop targeted drugs\, critica
 l in our fight against the emergence of widespread antibiotic resistance.\
 n\nBio: Institute of Structural and Molecular Biology (ISMB)\nPostdoctoral
  Research Scientist\nSep 2014 – Present\n\nPostdoctoral research positio
 n in the group of Professor Gabriel Waksman at the ISMB at Birkbeck Colleg
 e (University of London). My research is focused on Chaperone-Usher (CU) P
 ili of uropathogenic Escherichia coli\, a bacterial pathogen that is respo
 nsible for ~80% of urinary tract infections. Our aims are to illucidate th
 e structure of CU pili and to understand how these appendages are produced
  by the E. coli.\n\nPhD\, University of Cambridge\nMolecular Biology\, Bio
 chemistry\, Structural Biology\n2010 – 2014
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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