Open AccessProtein folding: How the mechanism of GroEL action is defined by kinetics
Author(s) -
Carl Frieden,
Clark Ac
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.11.5535
Subject(s) - groel , groes , protein folding , chaperonin , biophysics , foldase , chaperone (clinical) , chemistry , dissociation (chemistry) , atp hydrolysis , kinetics , folding (dsp implementation) , crystallography , biochemistry , biology , enzyme , escherichia coli , physics , medicine , atpase , pathology , quantum mechanics , electrical engineering , gene , engineering
We propose a mechanism for the role of the bacterial chaperonin GroEL in folding proteins. The principal assumptions of the mechanism are (i ) that many unfolded proteins bind to GroEL because GroEL preferentially binds small unstructured regions of the substrate protein, (ii ) that substrate protein within the cavity of GroEL folds by the same kinetic mechanism and rate processes as in bulk solution, (iii ) that stable or transient complexes with GroEL during the folding process are defined by a kinetic partitioning between formation and dissociation of the complex and the rate of folding and unfolding of the protein, and (iv ) that dissociation from the complex in early stages of folding may lead to aggregation but dissociation at a late stage leads to correct folding. The experimental conditions for refolding may play a role in defining the function of GroEL in the folding pathway. We propose that the role of GroES and MgATP, either binding or hydrolysis, is to regulate the association and dissociation processes rather than affecting the rate of folding.