GroEL-mediated folding of structurally homologous dihydrofolate reductases

Journal of Molecular Biology
A C Clark, C Frieden

Abstract

Using stopped-flow fluorescence techniques, we have examined both the refolding and unfolding reactions of four structurally homologous dihydrofolate reductases (murine DHFR, wild-type E. coli DHFR, and two E. coli DHFR mutants) in the presence and absence of the molecular chaperonin GroEL. We show that GroEL binds the unfolded conformation of each DHFR with second order rate constants greater than 3 x 10(7) M(-1)s(-1) at 22 degrees C. Once bound to GroEL, the proteins refold with rate constants similar to those for folding in the absence of GroEL. The overall rate of formation of native enzyme is decreased by the stability of the complex between GroEL and the last folding intermediate. For wild-type E. coli DHFR, complex formation is transient while for the others, a stable complex is formed. The stable complexes are the same regardless of whether they are formed from the unfolded or folded DHFR. When complex formation is initiated from the native conformation, GroEL binds to a pre-existing non-native conformation, presumably a late folding intermediate, rather than to the native state, thus shifting the conformational equilibrium toward the non-native species by mass action. The model presented here for the interaction of the...Continue Reading

References

Dec 2, 1975·Biochemistry·D BaccanariJ Burchall
Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·C Frieden
Nov 7, 1995·Biochemistry·L S ItzhakiA R Fersht
Jul 28, 1995·Journal of Molecular Biology·N A RansonA R Clarke
Sep 15, 1995·The Journal of Biological Chemistry·K E Smith, M T Fisher
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·H Lilie, J Buchner
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·F J Corrales, A R Fersht
Aug 20, 1993·Journal of Molecular Biology·T E Gray, A R Fersht
Feb 1, 1996·Nature Structural Biology·D C BoisvertP B Sigler
Jan 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R J Ellis, F U Hartl
Jan 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G H Lorimer
Apr 26, 1996·Journal of Molecular Biology·H SparrerJ Buchner
May 24, 1996·Journal of Molecular Biology·K KatsumataK Kuwajima
Mar 5, 1996·Proceedings of the National Academy of Sciences of the United States of America·Z Lin, E Eisenstein
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·S WalterF X Schmid
Mar 1, 1996·Protein Science : a Publication of the Protein Society·A Ayling, F Baneyx
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·P GervasoniA Plückthun
Dec 1, 1996·Protein Science : a Publication of the Protein Society·M GrossS E Radford
Jan 1, 1996·Folding & Design·R J Ellis

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Citations

Mar 19, 1999·Protein Science : a Publication of the Protein Society·F DoñateM Martinez-Carrion
Sep 27, 2000·Cell Stress & Chaperones·M D de BeusC M Teschke
Jul 1, 2009·International Journal of Molecular Sciences·Victor V Marchenkov, Gennady V Semisotnov
May 27, 1997·Proceedings of the National Academy of Sciences of the United States of America·C Frieden, A C Clark
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·O Yifrach, A Horovitz
Nov 21, 1998·Molecular Microbiology·L K Anderson, C M Toole
Apr 28, 2009·Journal of Molecular Biology·Ashish K Patra, Jayant B Udgaonkar
Oct 15, 2005·Physical Biology·Huan-Xiang Zhou
Mar 25, 2006·Organic & Biomolecular Chemistry·Huw JonesAndrew D Miller
Jul 20, 2006·Critical Reviews in Biochemistry and Molecular Biology·Zong Lin, Hays S Rye
Aug 31, 2001·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Y D ParkH M Zhou
Nov 22, 2001·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·W A Houry
Nov 21, 1998·The Journal of Biological Chemistry·O KopsM Tropschug
Aug 29, 1998·The Journal of Biological Chemistry·J R MattinglyM Martinez-Carrion
Dec 16, 1998·The Journal of Biological Chemistry·J D Andreadis, L W Black
Sep 17, 1998·The Journal of Biological Chemistry·P A VoziyanM T Fisher
Nov 30, 2018·Frontiers in Molecular Biosciences·Paul E SchavemakerBert Poolman
Jul 11, 2001·Biochemical and Biophysical Research Communications·S ZhangC C Wang
Mar 31, 1998·Current Opinion in Structural Biology·A Horovitz
Mar 15, 2000·The International Journal of Biochemistry & Cell Biology·M F Mouat
Jan 1, 1997·Folding & Design·J E CoyleS E Radford

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