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SUMMARY:Host matrix-pathogen interactions and redox sensing\; tandem beta-
 zippers and &quot\;inside-out&quot\; protein-protein recognition. -  Dr. J
 ennifer Potts  University of York
DTSTART:20101103T103000Z
DTEND:20101103T113000Z
UID:TALK27029@talks.cam.ac.uk
CONTACT:Dr Alfonso De Simone
DESCRIPTION:The interaction between Staphylococcus aureus and Streptococcu
 s pyogenes with the human plasma and extracellular matrix protein fibronec
 tin triggers bacterial invasion of host cells. This process has been propo
 sed to aid haematogenous dissemination of infection and evasion of the hos
 t immune system. We have used a range of biophysical techniques to define 
 the binding sites in the host and bacterial proteins and the structure of 
 the complex that forms. In a highly unusual mechanism of protein-protein r
 ecognition\, the bacterial peptide undergoes a transition from an intrinsi
 cally disordered state\, to an extended anti-parallel β-strand along the 
 triple-stranded β-sheets of up to five sequential fibronectin modules (1-
 3). A dissection of the S. aureus and S. pyogenes fibronectin-binding prot
 eins\, based on the tandem β-zipper and confirmed using isothermal titrat
 ion calorimetry\, has identified multiple high affinity binding sites in b
 oth proteins (4\,5). \nIn a separate project\, we have been investigating 
 a redox-sensing anti-sigma factor (RsrA) from Streptomyces coelicolor. We 
 have determined the solution structures of the reduced and oxidized forms 
 of RsrA. Comparison with the structures of homologous anti-sigma factors i
 n complex with their cognate sigma factors suggests another unusual mechan
 ism of protein-protein recognition.\n\n1.	Schwarz-Linek et al. (2003) Natu
 re 423\, 177-181\n2.	Bingham et al. (2008) Proc. Natl Acad. Sci. USA 105\,
  12254-12258\n3.	Atkin et al.\, (2010) J. Biol. Chem. (in press)\n4.	Schwa
 rz-Linek et al. (2004) J. Biol. Chem. 279\, 39017-39025\n5.	Meenan et al. 
 (2007) J. Biol. Chem. 282\, 25893-25902\n
LOCATION:Unilever Lecture Theatre\,  Department of Chemistry
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