Theoretical Physics Colloquium
Growth of Amyloid Fibrils
by Dr. Govardhan Reddy (University of Maryland, USA)
Monday, December 5, 2011
from
to
(Asia/Kolkata)
at Colaba Campus ( AG80 )
at Colaba Campus ( AG80 )
Description |
Proteins form structured aggregates known as amyloid fibrils. The growth mechanisms of amyloid fibrils, which are implicated in a number of neurodegenerative diseases, are poorly understood. We have performed extensive all-atom molecular dynamics simulations to study the structural changes that occur in a random coil protein fragment from the yeast prion Sup35 and Aβ-peptide upon interaction with a preformed fibril. We show that the random coil to β-strand transition in the protein fragment as it becomes a part of the fibril occurs abruptly over a very narrow time interval. Amyloid fibrils further adopt a cross-β-spine structure in which the two β-sheets fully interdigitate to create a dry interface. Formation of such a dry interface is usually associated with self-assembly of extended hydrophobic surfaces. We studied the role of water and mechanistic differences in the dry interface formation between β-sheets formed from vastly different peptide sequences, one a polar sequence from the yeast prion Sup35 and the other a predominantly hydrophobic sequence from the Aβ-peptide. |