Molecular crowding enhances native state stability and refolding rates of globular proteins Export

@article{citeulike:877227, abstract = {10.1073/pnas.0409630102 The presence of macromolecules in cells geometrically restricts the available space for poplypeptide chains. To study the effects of macromolecular crowding on folding thermodynamics and kinetics, we used an off-lattice model of the all-β-sheet WW domain in the presence of large spherical particles whose interaction with the polypeptide chain is purely repulsive. At all volume fractions, ϕ, of the crowding agents the stability of the native state is enhanced. Remarkably, the refolding rates, which are larger than the value at ϕ = 0, increase nonmonotonically as ϕ increases, reaching a maximum at . At high values of ϕ, the depletion-induced intramolecular attraction produces compact structures with considerable structure in the denatured state. Changes in native state stability and folding kinetics at ϕ can be quantitatively mapped onto confinement in a volume-fraction-dependent spherical pore with radius ≈ (4π/3ϕ) ( is the radius of the crowding particles) as long as . We show that the extent of native state stabilization at finite ϕ is comparable with that in a spherical pore. In both situations, rate enhancement is due to destabilization of the denatured states with respect to ϕ = 0.}, author = {Cheung, Margaret S. and Klimov, Dmitri and Thirumalai, D.}, citeulike-article-id = {877227}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0409630102}, citeulike-linkout-1 = {http://www.pnas.org/content/102/13/4753.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/102/13/4753.full.pdf}, citeulike-linkout-3 = {http://www.pnas.org/cgi/content/abstract/102/13/4753}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/15781864}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=15781864}, comment = {molecular crowding enhances stablility of proteins; off-lattice beta }, day = {29}, doi = {10.1073/pnas.0409630102}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, month = {March}, number = {13}, pages = {4753--4758}, posted-at = {2006-09-29 09:21:50}, priority = {2}, title = {Molecular crowding enhances native state stability and refolding rates of globular proteins}, url = {http://dx.doi.org/10.1073/pnas.0409630102}, volume = {102}, year = {2005} }

TY - JOUR ID - citeulike:877227 L3 - citeulike-article-id:877227 N2 - 10.1073/pnas.0409630102 The presence of macromolecules in cells geometrically restricts the available space for poplypeptide chains. To study the effects of macromolecular crowding on folding thermodynamics and kinetics, we used an off-lattice model of the all-β-sheet WW domain in the presence of large spherical particles whose interaction with the polypeptide chain is purely repulsive. At all volume fractions, ϕ, of the crowding agents the stability of the native state is enhanced. Remarkably, the refolding rates, which are larger than the value at ϕ = 0, increase nonmonotonically as ϕ increases, reaching a maximum at . At high values of ϕ, the depletion-induced intramolecular attraction produces compact structures with considerable structure in the denatured state. Changes in native state stability and folding kinetics at ϕ can be quantitatively mapped onto confinement in a volume-fraction-dependent spherical pore with radius ≈ (4π/3ϕ) ( is the radius of the crowding particles) as long as . We show that the extent of native state stabilization at finite ϕ is comparable with that in a spherical pore. In both situations, rate enhancement is due to destabilization of the denatured states with respect to ϕ = 0. IS - 13 JF - Proceedings of the National Academy of Sciences of the United States of America EP - 4758 TI - Molecular crowding enhances native state stability and refolding rates of globular proteins VL - 102 SP - 4753 N1 - molecular crowding enhances stablility of proteins; off-lattice beta AU - Cheung, Margaret AU - Klimov, Dmitri AU - Thirumalai, D PY - 2005/03/29/ UR - http://dx.doi.org/10.1073/pnas.0409630102 ER -