Solution structure, dynamics, and thermodynamics of the native state ensemble of the Sem-5 C-terminal SH3 domain

Josephine C. Ferreon, David E. Volk, Bruce A. Luxon, David G. Gorenstein, Vincent J. Hilser

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    Although the high-resolution structure of a protein may provide significant insight into which regions are important for function, it is well-known that proteins undergo significant conformational fluctuations, even under native conditions. This suggests that the static structure alone may not provide sufficient information for elucidation of the thermodynamic determinants of biological function and that an accurate molecular-level description of function requires knowledge of the nature and energetics of the conformational states that constitute the native state ensemble. Here the native state ensemble of the C-terminal src homology domain-3 (C-SH3) from Caenorhabditis elegans Sem-5 has been studied using a variety of high-resolution biophysical techniques. In addition to determining the first solution structure of the unliganded protein, we have performed 15N relaxation and native state hydrogen-deuterium exchange. It is observed that the regions of greatest structural variabilility also show low protection and order parameters, suggesting a higher degree of conformational diversity. These flexible regions also coincide with those regions of Sem-5 that have been predicted by the COREX algorithm to be unfolded in many of the most probable conformational states within the native state ensemble. The implications of this agreement and the potential role of conformational heterogeneity of the observed biophysical properties are discussed.

    Original languageEnglish (US)
    Pages (from-to)5582-5591
    Number of pages10
    JournalBiochemistry
    Volume42
    Issue number19
    DOIs
    StatePublished - May 20 2003

    Fingerprint

    src Homology Domains
    Thermodynamics
    Proteins
    Deuterium
    Caenorhabditis elegans
    Hydrogen

    ASJC Scopus subject areas

    • Biochemistry

    Cite this

    Ferreon, J. C., Volk, D. E., Luxon, B. A., Gorenstein, D. G., & Hilser, V. J. (2003). Solution structure, dynamics, and thermodynamics of the native state ensemble of the Sem-5 C-terminal SH3 domain. Biochemistry, 42(19), 5582-5591. https://doi.org/10.1021/bi030005j

    Solution structure, dynamics, and thermodynamics of the native state ensemble of the Sem-5 C-terminal SH3 domain. / Ferreon, Josephine C.; Volk, David E.; Luxon, Bruce A.; Gorenstein, David G.; Hilser, Vincent J.

    In: Biochemistry, Vol. 42, No. 19, 20.05.2003, p. 5582-5591.

    Research output: Contribution to journalArticle

    Ferreon, JC, Volk, DE, Luxon, BA, Gorenstein, DG & Hilser, VJ 2003, 'Solution structure, dynamics, and thermodynamics of the native state ensemble of the Sem-5 C-terminal SH3 domain', Biochemistry, vol. 42, no. 19, pp. 5582-5591. https://doi.org/10.1021/bi030005j
    Ferreon, Josephine C. ; Volk, David E. ; Luxon, Bruce A. ; Gorenstein, David G. ; Hilser, Vincent J. / Solution structure, dynamics, and thermodynamics of the native state ensemble of the Sem-5 C-terminal SH3 domain. In: Biochemistry. 2003 ; Vol. 42, No. 19. pp. 5582-5591.
    @article{f80f6c74399b4ef4ad232841c01f02e7,
    title = "Solution structure, dynamics, and thermodynamics of the native state ensemble of the Sem-5 C-terminal SH3 domain",
    abstract = "Although the high-resolution structure of a protein may provide significant insight into which regions are important for function, it is well-known that proteins undergo significant conformational fluctuations, even under native conditions. This suggests that the static structure alone may not provide sufficient information for elucidation of the thermodynamic determinants of biological function and that an accurate molecular-level description of function requires knowledge of the nature and energetics of the conformational states that constitute the native state ensemble. Here the native state ensemble of the C-terminal src homology domain-3 (C-SH3) from Caenorhabditis elegans Sem-5 has been studied using a variety of high-resolution biophysical techniques. In addition to determining the first solution structure of the unliganded protein, we have performed 15N relaxation and native state hydrogen-deuterium exchange. It is observed that the regions of greatest structural variabilility also show low protection and order parameters, suggesting a higher degree of conformational diversity. These flexible regions also coincide with those regions of Sem-5 that have been predicted by the COREX algorithm to be unfolded in many of the most probable conformational states within the native state ensemble. The implications of this agreement and the potential role of conformational heterogeneity of the observed biophysical properties are discussed.",
    author = "Ferreon, {Josephine C.} and Volk, {David E.} and Luxon, {Bruce A.} and Gorenstein, {David G.} and Hilser, {Vincent J.}",
    year = "2003",
    month = "5",
    day = "20",
    doi = "10.1021/bi030005j",
    language = "English (US)",
    volume = "42",
    pages = "5582--5591",
    journal = "Biochemistry",
    issn = "0006-2960",
    publisher = "American Chemical Society",
    number = "19",

    }

    TY - JOUR

    T1 - Solution structure, dynamics, and thermodynamics of the native state ensemble of the Sem-5 C-terminal SH3 domain

    AU - Ferreon, Josephine C.

    AU - Volk, David E.

    AU - Luxon, Bruce A.

    AU - Gorenstein, David G.

    AU - Hilser, Vincent J.

    PY - 2003/5/20

    Y1 - 2003/5/20

    N2 - Although the high-resolution structure of a protein may provide significant insight into which regions are important for function, it is well-known that proteins undergo significant conformational fluctuations, even under native conditions. This suggests that the static structure alone may not provide sufficient information for elucidation of the thermodynamic determinants of biological function and that an accurate molecular-level description of function requires knowledge of the nature and energetics of the conformational states that constitute the native state ensemble. Here the native state ensemble of the C-terminal src homology domain-3 (C-SH3) from Caenorhabditis elegans Sem-5 has been studied using a variety of high-resolution biophysical techniques. In addition to determining the first solution structure of the unliganded protein, we have performed 15N relaxation and native state hydrogen-deuterium exchange. It is observed that the regions of greatest structural variabilility also show low protection and order parameters, suggesting a higher degree of conformational diversity. These flexible regions also coincide with those regions of Sem-5 that have been predicted by the COREX algorithm to be unfolded in many of the most probable conformational states within the native state ensemble. The implications of this agreement and the potential role of conformational heterogeneity of the observed biophysical properties are discussed.

    AB - Although the high-resolution structure of a protein may provide significant insight into which regions are important for function, it is well-known that proteins undergo significant conformational fluctuations, even under native conditions. This suggests that the static structure alone may not provide sufficient information for elucidation of the thermodynamic determinants of biological function and that an accurate molecular-level description of function requires knowledge of the nature and energetics of the conformational states that constitute the native state ensemble. Here the native state ensemble of the C-terminal src homology domain-3 (C-SH3) from Caenorhabditis elegans Sem-5 has been studied using a variety of high-resolution biophysical techniques. In addition to determining the first solution structure of the unliganded protein, we have performed 15N relaxation and native state hydrogen-deuterium exchange. It is observed that the regions of greatest structural variabilility also show low protection and order parameters, suggesting a higher degree of conformational diversity. These flexible regions also coincide with those regions of Sem-5 that have been predicted by the COREX algorithm to be unfolded in many of the most probable conformational states within the native state ensemble. The implications of this agreement and the potential role of conformational heterogeneity of the observed biophysical properties are discussed.

    UR - http://www.scopus.com/inward/record.url?scp=0013298211&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0013298211&partnerID=8YFLogxK

    U2 - 10.1021/bi030005j

    DO - 10.1021/bi030005j

    M3 - Article

    VL - 42

    SP - 5582

    EP - 5591

    JO - Biochemistry

    JF - Biochemistry

    SN - 0006-2960

    IS - 19

    ER -