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Specific features of the prion protein transmembrane domain regulate nascent chain orientation.

Specific features of the prion protein transmembrane domain regulate nascent chain orientation. Research Abstract Details 

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  • Specific features of the prion protein transmembrane domain regulate nascent chain orientation. Abstract Text:

    carolyn m ottCarolyn M Ott,armin akhavanArmin Akhavan,vishwanath r lingappaVishwanath R Lingappa,

    The sequence of a transmembrane (TM) domain and the adjacent regions are important for recognition, orientation, and integration at the translocon during membrane protein biosynthesis. However, the sequences of individual TM domains vary considerably. Although some general effects of electrostatic and hydrophobic interactions have been observed, it is still not clear what features of diverse sequences influence TM domain orientation. Here we utilized the ability of the prion protein (PrP) to be synthesized in multiple topological forms to assay the effects of substitutions and mutations on TM domain orientation. Several of the TM domains we tested appear to contain no inherent information regulating orientation. In contrast, we found that the middle region of the PrP TM domain significantly reduces the ability of the chain to invert its orientation in the translocon. We also observed that the C-terminal region of the PrP TM domain influences orientation, and we characterized the orientation differences between two forms of a physiologically relevant polymorphism in this region. Specifically, we found that the identity of a single amino acid, that at position 129, can significantly alter PrP TM domain orientation. Because position 129 is the location of the disease-associated Met/Val polymorphism, we discuss both how this small change may affect TMD orientation and the larger biological implications of these results.

    Specific features of the prion protein transmembrane domain regulate nascent chain orientation. Publishing Authors By Initials

    cm ottCM Ott,a akhavanA Akhavan,vr lingappaVR Lingappa,

    For similar proteins: prions research abstracts see: proteins: prions research

    PUBMED ID PMID:

    MEDLINE DATE:

    Specific features of the prion protein transmembrane domain regulate nascent chain orientation. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: The Journal of biological chemistry

    VOLUME: 282

    Page Numbers: 11163-71

    Journal Abbreviation:

    ISSN: 0021-9258

    DAY: 2

    MONTH: 02

    YEAR: 2007

    Specific features of the prion protein transmembrane domain regulate nascent chain orientation. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 2985121

    Specific features of the prion protein transmembrane domain regulate nascent chain orientation. Keywords Mesh Terms:

    KEYWORDS: Prions

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Specific features of the prion protein transmembrane domain regulate nascent chain orientation. Information

    Substance Name: Methionine

    Registry Number: 63-68-3

    Grant and Affiliation Information for Specific features of the prion protein transmembrane domain regulate nascent chain orientation.

    AFFILIATION: Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NINDS

    GRANT: NS37365

    ACRONYM: NS

    MEDLINETA: J Biol Chem

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

    Number Hits: 0

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