Characterizing methyl-bearing side chain contacts and dynamics mediating amyloid β protofibril interactions using ¹³C(methyl)-DEST and lifetime line broadening

Nicolas L. Fawzi, David S. Libich, Jinfa Ying, Vitali Tugarinov, G. Marius Clore

Resultado de la investigación: Articlerevisión exhaustiva

37 Citas (Scopus)

Resumen

Many details pertaining to the formation and interactions of protein aggregates associated with neurodegenerative diseases are invisible to conventional biophysical techniques. We recently introduced (15)N dark-state exchange saturation transfer (DEST) and (15)N lifetime line-broadening to study solution backbone dynamics and position-specific binding probabilities for amyloid β (Aβ) monomers in exchange with large (2-80 MDa) protofibrillar Aβ aggregates. Here we use (13)C(methyl)DEST and lifetime line-broadening to probe the interactions and dynamics of methyl-bearing side chains in the Aβ-protofibril-bound state. We show that all methyl groups of Aβ40 populate direct-contact bound states with a very fast effective transverse relaxation rate, indicative of side-chain-mediated direct binding to the protofibril surface. The data are consistent with position-specific enhancements of (13)C(methyl)-R₂(tethered) values in tethered states, providing further insights into the structural ensemble of the protofibril-bound state.

Idioma originalEnglish (US)
Páginas (desde-hasta)10345-10349
Número de páginas5
PublicaciónAngewandte Chemie (International ed. in English)
Volumen53
N.º39
DOI
EstadoPublished - sept. 22 2014
Publicado de forma externa

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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