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Biophysical Studies of Amyloid Formation and Its Inhibition
Author(s) -
Radford Sheena
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.491.1
Subject(s) - amyloid (mycology) , amyloid disease , chemistry , small molecule , protein aggregation , amyloid fibril , biophysics , computational biology , biochemistry , amyloid β , biology , disease , medicine , inorganic chemistry , pathology
Amyloid formation involves the self‐association of proteins and peptides into polymers with a cross‐ß fold. How amyloid formation causes disease, and identifying the culprit species involved, remain a significant challenge. This results from the complexity of the aggregation process and the fact that amyloid assembly is initiated by non‐native states of proteins that are partially folded or intrinsically disordered. Structure determination is thus difficult, and identifying the interacting surfaces in these transiently formed and dynamic ensembles is challenging. In this lecture I will describe our recent attempts to discover new insights into how proteins aggregate into amyloid, and how to prevent amyloid assembly, using NMR and native mass spectrometry (MS). Specifically, I will show how NMR can be used to map the nature of the earliest protein‐protein interactions that result in amyloid assembly, and how MS methods can be used to screen for small molecules able to prevent aggregation and to map the species to which they bind