Prion Protein-Detergent Micelle Interactions Studied by NMR in Solution

Cellular prion proteins, PrPC, carrying the amino acid substitutions P102L, P105L, or A117V, which confer increased susceptibility to human transmissible spongiform encephalopathies, are known to form structures that include transmembrane polypeptide segments. Herein, we investigated the interaction...

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Bibliographic Details
Published in:The Journal of biological chemistry 2009-08, Vol.284 (34), p.22713-22721
Main Authors: Hornemann, Simone, von Schroetter, Christine, Damberger, Fred F., Wüthrich, Kurt
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Detergents - chemistry
Magnetic Resonance Spectroscopy - methods
Membrane Transport, Structure, Function, and Biogenesis
Mice
Micelles
Molecular Sequence Data
Phosphorylcholine - analogs & derivatives
Phosphorylcholine - chemistry
Prions - chemistry
Sequence Homology, Amino Acid
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Summary:Cellular prion proteins, PrPC, carrying the amino acid substitutions P102L, P105L, or A117V, which confer increased susceptibility to human transmissible spongiform encephalopathies, are known to form structures that include transmembrane polypeptide segments. Herein, we investigated the interactions between dodecylphosphocholine micelles and the polypeptide fragments 90–231 of the recombinant mouse PrP variants carrying the amino acid replacements P102L, P105L, A117V, A113V/A115V/A118V, K110I/H111I, M129V, P105L/M129V, and A117V/M129V. Wild-type mPrP-(90–231) and mPrP[M129V]-(91–231) showed only weak interactions with dodecylphosphocholine micelles in aqueous solution at pH 7.0, whereas discrete interaction sites within the polypeptide segment 102–127 were identified for all other aforementioned mPrP variants by NMR chemical shift mapping. These model studies thus provide evidence that amino acid substitutions within the polypeptide segment 102–127 affect the interactions of PrPC with membranous structures, which might in turn modulate the physiological function of the protein in health and disease.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109.000430