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Amyloids and Prions: structure, conformations and conformational transitions as seen by NMR
Author(s) -
Meier Beat H,
Verel Rene,
Steinmetz Michel,
Siemer Ansgar B,
Köneke Stephanie,
Lange Adam,
Melckebeke Helene,
Wasmer Christian,
Ernst Matthias
Publication year - 2007
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.21.5.a96
Subject(s) - antiparallel (mathematics) , chemistry , amyloid fibril , molecular dynamics , protein structure , conformational ensembles , nuclear magnetic resonance spectroscopy , podospora anserina , crystallography , stereochemistry , mutant , computational chemistry , physics , biochemistry , amyloid β , medicine , disease , pathology , quantum mechanics , magnetic field , gene
While, at the time of the writing of this abstract, no atomic resolution structure of an amyloid fibril is available, considerable progress has been made towards this aim by a number of research groups. Solid‐state NMR has the potential to be a key method in this respect. Beyond the mere structure determination, NMR also allows to describe the degree of molecular order and the molecular dynamics on a residue‐by‐residue basis. This information can be used to characterize the nature and the kinetics of conformational transitions. The talk will describe work from the authors lab and will concentrate on two specific systems: A de novo designed 17‐mer (SIRELEARIRELELRIG) which can be switched between a coiled‐coil and an amyloid conformation by a temperature jump and shows many of the properties of amyloids related to neurodegenerative diseases. This system consists of antiparallel beta sheets. Depending on pH, one of two forms, related by a shift in register of 5 amino acids, is formed. The structure as well as the interconversion dynamics and the interconversion mechanism will be discussed. The HET‐s prion protein from the fungus podospora anserina . The HET‐s is special with respect to its spectral properties because the lines are narrower than in other prions and amyloids, indicating high local order for the core of the fibrils. The loop and head/tail region, however, are dynamically and/or statically disordered. We will discuss these properties in detail and will describe progress towards atomic‐resolution structure determination. The relationship between structure and infectivity will also be discussed.