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Temperature and urea have opposing impacts on polyproline II conformational bias.
Elam, W Austin; Schrank, Travis P; Campagnolo, Andrew J; Hilser, Vincent J.
Afiliação
  • Elam WA; T. C. Jenkins Department of Biophysics and Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States.
Biochemistry ; 52(5): 949-58, 2013 Feb 05.
Article em En | MEDLINE | ID: mdl-23350874
The native states of globular proteins have been accessed in atomic detail by X-ray crystallography and nuclear magnetic resonance spectroscopy, yet characterization of denatured proteins beyond global metrics has proven to be elusive. Denatured proteins have been observed to exhibit global geometric properties of a random coil polymer. However, this does not preclude the existence of nonrandom, local conformational bias that may be significant for protein folding and function. Indeed, circular dichroism (CD) spectroscopy and other methods have suggested that the denatured state contains considerable local bias to the polyproline II (PII) conformation. Here, we develop predictive models to determine the extent that temperature and the chemical denaturant urea modulate PII propensity. In agreement with our predictive model, PII propensity is observed experimentally to decrease with an increase in temperature. Conversely, urea appears to promote the PII conformation as determined by CD and isothermal titration calorimetry. Importantly, the calorimetric data are in quantitative agreement with a model that predicts the stability of the PII helix relative to other denatured state conformations based upon solvent accessible surface area and experimentally measured Gibbs transfer free energies. The ability of urea to promote the PII conformation can be attributed to the favorable interaction of urea with the peptide backbone. Thus, perturbing denatured states by temperature or cosolutes has subtle, yet opposing, impacts on local PII conformational biases. These results have implications for protein folding as well as for the function of signaling proteins that bind proline-rich targets in globular or intrinsically disordered proteins.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos / Ureia / Caenorhabditis elegans / Proteínas Son Of Sevenless / Proteínas de Caenorhabditis elegans Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Biochemistry Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Peptídeos / Ureia / Caenorhabditis elegans / Proteínas Son Of Sevenless / Proteínas de Caenorhabditis elegans Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Biochemistry Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Estados Unidos