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SUMMARY:Antibody binding regulates the dynamics of the cellular prion prot
ein - Dr Ioana Ilie\, University of Amsterdam
DTSTART:20221114T143000Z
DTEND:20221114T150000Z
UID:TALK192416@talks.cam.ac.uk
CONTACT:Jerelle Joseph
DESCRIPTION:Prion diseases are associated with the conversion of the cellu
lar prion protein (PrPC) into a pathogenic conformer (PrPS
c). A proposed therapeutic approach to avoid the pathogenic transfor
mation is to develop monoclonal antibodies that bind to PrPC an
d stabilize its structure. POM1 and POM6 are two monoclonal antibodies tha
t bind the globular domain of PrPC and have different biologica
l responses\, i.e. trigger neurotoxicity mimicking prion infections (POM1)
or prevent neurotoxicity (POM6). The crystal structures of PrPC in complex with the two antibodies show similar epitopes which seems inc
onsistent with the opposite phenotypes.\nHere\, we investigate the influen
ce of the POM1 and POM6 antibodies on the flexibility and the interaction
with the membrane of the mouse PrPC by molecular dynamics simul
ations. The results show that in the presence of any of the two antibodies
\, the flexibility of the globular domain increases everywhere except for
the ß1-α1 loop in the POM1/PrPC complex\, which is part of it
s epitope [1]. Additionally\, the binding of the antibodies restricts the
range of orientations of the globular domain with respect to the membrane\
, decreases the distance between both modules of PrPC and the m
embrane\, and restricts the orientational disorder of the globular domain.
Furthermore\, the interactions of the flexible tail and globular domain a
re modulated differently by the two antibodies [2].\n\n[1] ILIE & Caflisch
\, BBA-Proteins Proteom. 1870\, 140827 (2022)\n[2] ILIE et al. Biophys. J.
121\, 2813 (2022)
LOCATION:Zoom
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