Monitoring Protein Conformation along the Pathway of Chaperonin-Assisted Folding

@article{citeulike:2648752, abstract = {Summary The GroEL/GroES chaperonin system mediates protein folding in the bacterial cytosol. Newly synthesized proteins reach GroEL via transfer from upstream chaperones such as DnaK/DnaJ (Hsp70). Here we employed single molecule and ensemble FRET to monitor the conformational transitions of a model substrate as it proceeds along this chaperone pathway. We find that DnaK/DnaJ stabilizes the protein in collapsed states that fold exceedingly slowly. Transfer to GroEL results in unfolding, with a fraction of molecules reaching locally highly expanded conformations. ATP-induced domain movements in GroEL cause transient further unfolding and rapid mobilization of protein segments with moderate hydrophobicity, allowing partial compaction on the GroEL surface. The more hydrophobic regions are released upon subsequent protein encapsulation in the central GroEL cavity by GroES, completing compaction and allowing rapid folding. Segmental chain release and compaction may be important in avoiding misfolding by proteins that fail to fold efficiently through spontaneous hydrophobic collapse.}, author = {Sharma, Shruti and Chakraborty, Kausik and Muller, Barbara K. and Astola, Nagore and Tang, Yun-Chi and Lamb, Don C. and Hayer-Hartl, Manajit and Hartl, Ulrich F. }, citeulike-article-id = {2648752}, doi = {10.1016/j.cell.2008.01.048}, journal = {Cell}, keywords = {experiment, folding, fret, groel, protein}, month = {April}, number = {1}, pages = {142--153}, posted-at = {2008-05-14 07:28:04}, priority = {2}, title = {Monitoring Protein Conformation along the Pathway of Chaperonin-Assisted Folding}, url = {http://dx.doi.org/10.1016/j.cell.2008.01.048}, volume = {133}, year = {2008} }

TY - JOUR ID - citeulike:2648752 L3 - citeulike-article-id:2648752 TI - Monitoring Protein Conformation along the Pathway of Chaperonin-Assisted Folding JF - Cell VL - 133 IS - 1 SP - 142 EP - 153 N2 - Summary The GroEL/GroES chaperonin system mediates protein folding in the bacterial cytosol. Newly synthesized proteins reach GroEL via transfer from upstream chaperones such as DnaK/DnaJ (Hsp70). Here we employed single molecule and ensemble FRET to monitor the conformational transitions of a model substrate as it proceeds along this chaperone pathway. We find that DnaK/DnaJ stabilizes the protein in collapsed states that fold exceedingly slowly. Transfer to GroEL results in unfolding, with a fraction of molecules reaching locally highly expanded conformations. ATP-induced domain movements in GroEL cause transient further unfolding and rapid mobilization of protein segments with moderate hydrophobicity, allowing partial compaction on the GroEL surface. The more hydrophobic regions are released upon subsequent protein encapsulation in the central GroEL cavity by GroES, completing compaction and allowing rapid folding. Segmental chain release and compaction may be important in avoiding misfolding by proteins that fail to fold efficiently through spontaneous hydrophobic collapse. KW - experiment KW - folding KW - fret KW - groel KW - protein AU - Sharma, Shruti AU - Chakraborty, Kausik AU - Muller, Barbara AU - Astola, Nagore AU - Tang, Yun-Chi AU - Lamb, Don AU - Hayer-Hartl, Manajit AU - Hartl, Ulrich PY - 2008/04/04/ UR - http://dx.doi.org/10.1016/j.cell.2008.01.048 ER -