BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//talks.cam.ac.uk//v3//EN
BEGIN:VTIMEZONE
TZID:Europe/London
BEGIN:DAYLIGHT
TZOFFSETFROM:+0000
TZOFFSETTO:+0100
TZNAME:BST
DTSTART:19700329T010000
RRULE:FREQ=YEARLY;BYMONTH=3;BYDAY=-1SU
END:DAYLIGHT
BEGIN:STANDARD
TZOFFSETFROM:+0100
TZOFFSETTO:+0000
TZNAME:GMT
DTSTART:19701025T020000
RRULE:FREQ=YEARLY;BYMONTH=10;BYDAY=-1SU
END:STANDARD
END:VTIMEZONE
BEGIN:VEVENT
CATEGORIES:Lennard-Jones Centre
SUMMARY:Antibody binding regulates the dynamics of the cel
 lular prion protein - Dr Ioana Ilie\, University o
 f Amsterdam
DTSTART;TZID=Europe/London:20221114T143000
DTEND;TZID=Europe/London:20221114T150000
UID:TALK192416AThttp://talks.cam.ac.uk
URL:http://talks.cam.ac.uk/talk/index/192416
DESCRIPTION:Prion diseases are associated with the conversion 
 of the cellular prion protein (PrP<sup>C</sup>) in
 to a pathogenic conformer (PrP<sup>Sc</sup>). A pr
 oposed therapeutic approach to avoid the pathogeni
 c transformation is to develop monoclonal antibodi
 es that bind to PrP<sup>C</sup> and stabilize its 
 structure. POM1 and POM6 are two monoclonal antibo
 dies that bind the globular domain of PrP<sup>C</s
 up> and have different biological responses\, i.e.
  trigger neurotoxicity mimicking prion infections 
 (POM1) or prevent neurotoxicity (POM6). The crysta
 l structures of PrP<sup>C</sup> in complex with th
 e two antibodies show similar epitopes which seems
  inconsistent with the opposite phenotypes.\nHere\
 , we investigate the influence of the POM1 and POM
 6 antibodies on the flexibility and the interactio
 n with the membrane of the mouse PrP<sup>C</sup> b
 y molecular dynamics simulations. The results show
  that in the presence of any of the two antibodies
 \, the flexibility of the globular domain increase
 s everywhere except for the ß1-α1 loop in the POM1
 /PrP<sup>C</sup> complex\, which is part of its ep
 itope [1]. Additionally\, the binding of the antib
 odies restricts the range of orientations of the g
 lobular domain with respect to the membrane\, decr
 eases the distance between both modules of PrP<sup
 >C</sup> and the membrane\, and restricts the orie
 ntational disorder of the globular domain. Further
 more\, the interactions of the flexible tail and g
 lobular domain are modulated differently by the tw
 o antibodies [2].\n\n[1] ILIE & Caflisch\, BBA-Pro
 teins Proteom. 1870\, 140827 (2022)\n[2] ILIE et a
 l. Biophys. J. 121\, 2813 (2022)
LOCATION:Zoom
CONTACT:Jerelle Joseph
END:VEVENT
END:VCALENDAR