title: The push-and-pull hypothesis in protein unfolding, misfolding and aggregation.
abstract: The combination of biophysical and structural techniques has allowed the visualization of species classified as dry molten-globule states. Further destabilization causes these structures to follow through a wet-globule stage to reach an unfolded chain. We have recently combined small angle X-ray scattering and nuclear magnetic resonance to observe these species, and we introduce a push-and-pull hypothesis to explain the dissimilar actions of urea and high pressure on proteins. The implications of these molten-globule states are further discussed in light of their potential physiological and pathological roles, especially in protein misfolding diseases.
authors.affiliation: Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis, Instituto Nacional de Biologia Estrutural e Bioimagem, Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: gaugusto@bioqmed.ufrj.br.
authors.forename: Guilherme A P
authors.initials: GAP
authors.lastname: de Oliveira
authors.affiliation: Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis, Instituto Nacional de Biologia Estrutural e Bioimagem, Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: jerson@bioqmed.ufrj.br.
authors.forename: Jerson L
authors.initials: JL
authors.lastname: Silva
mesh_terms: D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D053838:Scattering, Small Angle; D014508:Urea / Q000737:chemistry; D014961:X-Ray Diffraction; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism
chemical_list: D011506:Proteins; D051844:alpha-Synuclein; D014508:Urea
keywords: Alpha-synuclein; High hydrostatic pressure; High-pressure spectroscopy; Molten globule; Protein misfolding; Urea; p53