title: Protein unfolding by biological unfoldases: insights from modeling.
abstract: The molecular determinants of the high efficiency of biological machines like unfoldases (e.g., the proteasome) are not well understood. We propose a model to study protein translocation into the chamber of biological unfoldases represented as a funnel. It is argued that translocation is a much faster way of unfolding a protein than end-to-end stretching, especially in a low-force regime, because it allows for a conformational freedom while concentrating local tension on consecutive regions of a protein chain and preventing refolding. This results in a serial unfolding of the protein structures dominated by unzipping. Thus, pulling against the unfoldase pore is an efficient catalyst of the unfolding reaction. We also show that the presence of the funnel makes the tension along the backbone of the substrate protein nonuniform even when the protein gets unfolded. Hence, the stalling force measured by single-molecule force spectroscopy techniques may be smaller than the traction force of the unfoldase motor.
authors.affiliation: Institute of Physics, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Wojciechowski
authors.affiliation: Institute of Theoretical Physics, Faculty of Physics, University of Warsaw, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Szymczak
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Cientificas and Instituto Madrileño de Estudios Avanzados en Nanociencia, Madrid, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Carrión-Vázquez
authors.affiliation: Institute of Physics, Polish Academy of Sciences, Warsaw, Poland. Electronic address: cieplak@ifpan.edu.pl.
authors.forename: Marek
authors.initials: M
authors.lastname: Cieplak
mesh_terms: D001696:Biomechanical Phenomena; D056004:Molecular Dynamics Simulation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011487:Protein Conformation; D021381:Protein Transport; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013057:Spectrum Analysis; D013314:Stress, Mechanical
chemical_list: D011506:Proteins; D046988:Proteasome Endopeptidase Complex