Protein folding: Independent unrelated pathways or predetermined pathway with optional errors

@article{citeulike:2821346, abstract = {The observation of heterogeneous protein folding kinetics has been widely interpreted in terms of multiple independent unrelated pathways (IUP model), both experimentally and in theoretical calculations. However, direct structural information on folding intermediates and their properties now indicates that all of a protein population folds through essentially the same stepwise pathway, determined by cooperative native-like foldon units and the way that the foldons fit together in the native protein. It is essential to decide between these fundamentally different folding mechanisms. This article shows, contrary to previous supposition, that the heterogeneous folding kinetics observed for the staphylococcal nuclease protein (SNase) does not require alternative parallel pathways. SNase folding kinetics can be fit equally well by a single predetermined pathway that allows for optional misfolding errors, which are known to occur ubiquitously in protein folding. Structural, kinetic, and thermodynamic information for the folding intermediates and pathways of many proteins is consistent with the predetermined pathway-optional error (PPOE) model but contrary to the properties implied in IUP models. 10.1073/pnas.0801864105}, author = {Bedard, Sabrina and Krishna, Mallela M. and Mayne, Leland and Englander, Walter S. }, citeulike-article-id = {2821346}, doi = {http://dx.doi.org/10.1073/pnas.0801864105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {folding, pathways, protein}, month = {May}, number = {20}, pages = {7182--7187}, posted-at = {2008-05-21 21:49:48}, priority = {2}, title = {Protein folding: Independent unrelated pathways or predetermined pathway with optional errors}, url = {http://dx.doi.org/10.1073/pnas.0801864105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:2821346 L3 - citeulike-article-id:2821346 N2 - The observation of heterogeneous protein folding kinetics has been widely interpreted in terms of multiple independent unrelated pathways (IUP model), both experimentally and in theoretical calculations. However, direct structural information on folding intermediates and their properties now indicates that all of a protein population folds through essentially the same stepwise pathway, determined by cooperative native-like foldon units and the way that the foldons fit together in the native protein. It is essential to decide between these fundamentally different folding mechanisms. This article shows, contrary to previous supposition, that the heterogeneous folding kinetics observed for the staphylococcal nuclease protein (SNase) does not require alternative parallel pathways. SNase folding kinetics can be fit equally well by a single predetermined pathway that allows for optional misfolding errors, which are known to occur ubiquitously in protein folding. Structural, kinetic, and thermodynamic information for the folding intermediates and pathways of many proteins is consistent with the predetermined pathway-optional error (PPOE) model but contrary to the properties implied in IUP models. 10.1073/pnas.0801864105 IS - 20 JF - Proceedings of the National Academy of Sciences EP - 7187 TI - Protein folding: Independent unrelated pathways or predetermined pathway with optional errors VL - 105 SP - 7182 KW - folding KW - pathways KW - protein AU - Bedard, Sabrina AU - Krishna, Mallela AU - Mayne, Leland AU - Englander, Walter PY - 2008/05/20/ UR - http://dx.doi.org/10.1073/pnas.0801864105 ER -