Biochemistry Online: An Approach Based on Chemical Logic

Biochemistry Online




Last Update:  3/1/16

Learning Goals/Objectives for Chapter 2D:  After class and this reading, students will be able to

  • differentiate between thermodynamic (equilibrium) and kinetic (timed) approaches to the study of protein folding reactions
  • describe techniques to study transient (kinetic) and long-lived (thermodynamic) intermediates in protein folding
  • describe the following intermediates in protein folding:  molten globule, X-Pro isomers; Disulfide bond intermediates
  • interpret spectral and chromatographic data from protein folding studies and use this to determine or explain a mechanism for folding
  • describe properties of folded, unfolded, molten globule, and intrinsically disordered proteins
  • explain the difference between the environments for protein folding when performed in vitro and in vivo
  • state the role of molecular chaperones in in vivo protein folding
  • describe differences in disulfide bond occurrence in cytoplasmic and extracellular proteins

D9.  Recent References

  1. F. Ulrich Hartl, Andreas Bracher & Manajit Hayer-Hartl.   Molecular chaperones in protein folding and proteostasis. Nature 475, 324-332 (2011) doi:10.1038/nature10317 
  2. Dunker, A et al. Intrinsically disordered proteins.   Journal of Molecular Graphics and Modeling.  19, 26 (2001)
  3. Dunker, A. et al. The unfoldomics decade: an update on intrinsically disordered proteins.BMC Genomics 2008, 9(Suppl 2):S1 doi:10.1186/1471-2164-9-S2-S1
  4. Schuck, S. et al. J. Cell Biol 187, 525 (2009)
  5. Riemer, J. et al. Disulfide Formation in the ER and Mitochondria:  Two Solutions to a Common Process. Science 324, 1284 (2009)
  6. Depuydt, M. et al.  A Periplasmic Reducing System Protects Single Cysteine Residues from Oxidation.  Science 326, 1109 (2009)
  7. Uversky, V & Dunker, A. Controlled Chaos.  Science.  320, 1340 (2008)
  8. Bemporad, F. et al. Biological function in a non-native partially folded state of a protein.  EMBO Journal  27, 1525 (2008)
  9. Murzin, A. Metamorphic Proteins.  Science 320, 1725 (2008)
  10. Kimchi-Sarfaty, C. et al. A "Silent Polymorphism in the MDR1 Gene Alters Substrate Specificity. Science 315, 525 (2007)
  11. Religa, T. et al. Solution Structure of a protein denatured state and folding intermediate.  Nature. 437, 1053 (2005)
  12. Cecconi et al. Direct Observation of the Three-State Folding of a Single Protein Molecule.  Science 309, 2057 (2005)
  13. Krantz, B.A. et al. A Phenylalanine Clamp Catalyzes Protein Translocation Through the Anthrax Toxin Pore.  Science 309, 777 (2005)
  14. Hessa, T. et al. Recognition of transmembrane helices by the endoplasmic reticulum translocon. Nature 433, 377 (2005)
  15. Bowie, J. U. Cell Biology: Border Crossing. Nature 433, 367 (2005)
  16. van den Berg, B et al. X-ray structure of a protein-conducting channel.  Nature, 427, pg 36 (2004)
  17. Dobson, C. Protein folding and misfolding. Nature. 426, pg 884 (2003)
  18. Kamal, A. et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors.  Nature. 425, pg 407, 357 (2003)
  19. Ishii, D et al. Chaperonin-mediated stabilization and ATP-triggered release of semiconductor nanoparticles. Nature. 423, pg 628 (2003)
  20. Hartl and Hartl. Molecular Chaperones in the Cytosol: from nascent chain to folded protein Sicence. 295, og 1852 (2002)
  21. Houry et al. Identification of in vivo substrates of the chaperonin GroEL.  Nature Nov 1999, pg 147. (Vol 402?)
  22. Vendruscolo  et al. Three key residues form a critical contact network in a protein folding transition state.  Nature 409, pg 641 (2001)
  23. Baker. A surprising simplicity to protein folding.  Nature. 405, pg 39 (2000)
  24. Batey et al. Crystal structure of the ribonucleoprotein core of the signal recognition particle. (which binds newly synthesized proteins cotranslationally, arrests the synthesis, and docks the particle to the endoplasmic reticulum where synthesis restarts and the protein is discharged into the ER lumen for movement elsewhere in the cell). Science. 287, pg 1232 (2000)
  25. Shin et al. Interaction of partially unfolded forms of Torpedo acetylcholinesterase with liposomes.  Protein Science. 5, pg 42 (1996)
  26. Ren et al. Interaction of diphtheria toxin T domain (transmembrane domain) with molten globule-like proteins and its implication for translocation. Science.  284. pg 955 (1999)
  27. Netzer and Hartl.  Recombination of protein domains facilitated by co-translational folding in eukaryotes.  Nature. 388, pg 329, 343 (1997)
  28. Weber-Ban et al. Global unfolding of a substrate protein (GFP) by the Hsp 100 chaperone ClpA.  Nature. 401, pg 29, 90 (1999)


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