Local cooperativity in the unfolding of an amyloidogenic variant of human lysozyme - PubMed (original) (raw)

Local cooperativity in the unfolding of an amyloidogenic variant of human lysozyme

Denis Canet et al. Nat Struct Biol. 2002 Apr.

Abstract

Hydrogen exchange experiments monitored by NMR and mass spectrometry reveal that the amyloidogenic D67H mutation in human lysozyme significantly reduces the stability of the beta-domain and the adjacent C-helix in the native structure. In addition, mass spectrometric data reveal that transient unfolding of these regions occurs with a high degree of cooperativity. This behavior results in the occasional population of a partially structured intermediate in which the three alpha-helices that form the core of the alpha-domain still have native-like structure, whereas the beta-domain and C-helix are simultaneously substantially unfolded. This finding suggests that the extensive intermolecular interactions that will be possible in such a species are likely to initiate the aggregation events that ultimately lead to the formation of the well-defined fibrillar structures observed in the tissues of patients carrying this mutation in the lysozyme gene.

PubMed Disclaimer

Publication types

MeSH terms

Substances

LinkOut - more resources