UZH-Logo

Maintenance Infos

Prion protein-detergent micelle interactions studied by NMR in solution


Hornemann, S; von Schroetter, C; Damberger, F F; Wüthrich, K (2009). Prion protein-detergent micelle interactions studied by NMR in solution. Journal of Biological Chemistry, 284(34):22713-22721.

Abstract

Cellular prion proteins, PrP(C), 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 PrP(C) with membranous structures, which might in turn modulate the physiological function of the protein in health and disease.

Cellular prion proteins, PrP(C), 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 PrP(C) with membranous structures, which might in turn modulate the physiological function of the protein in health and disease.

Citations

11 citations in Web of Science®
12 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

68 downloads since deposited on 03 Mar 2010
25 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2009
Deposited On:03 Mar 2010 17:35
Last Modified:26 Aug 2016 07:32
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in Journal of Biological Chemistry. 2009 Aug 21;284(34):22713-22721. Epub 2009 Jun 22. © the American Society for Biochemistry and Molecular Biology.
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1074/jbc.M109.000430
PubMed ID:19546219
Permanent URL: http://doi.org/10.5167/uzh-32076

Download

[img]
Preview
Content: Accepted Version
Filetype: PDF
Size: 1MB
View at publisher
[img]
Preview
Filetype: PDF
Size: 3MB

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations