Molecular Biophysics I
2005
Session #6

The Chaperonins
 (GroEL/ES & TRiC)

March 02, 2005
BMI 155-2
1:00 p.m. - 3:50 p.m.

The E. coli chaperonin GroEL/ES is one of the most fascinating of the molecular chaperone machines. Together, GroEL & GroES provide a sequestered environment for protein folding in the cell described as the "Anfinsen cage" or folding at "infinite dilution". As we shall see, present data suggest additional roles for this chaperonin in protein folding.

We also take a brief look at a group II chaperonin, represented by the eukaryotic cytosolic member TRiC.

The reference material is divided into two sections:

• Short comment papers Refs. #1 & #2 .
  
  These 'comment papers' can help familiarize you with the overall structure and terminology associated with GroEL & GroES, as well as assisting in the interpretation of the accompanying data papers. (Our course review papers provide additional information.)
   

• Data papers (Refs. #3 through #8) and a review paper on the chaperonin TRiC (Ref. #9).
  
  This selection of papers highlight important structural and functional properties of the GroEL/ES chaperonin. Due to their very nature, it will not be possible to cover all aspects of each paper.
  
  Therefore, please take careful note of the sections in each paper designated below for our class discussion. Concentrate your efforts on the designated figures and associated text (gloss over experimental details).
   

References

• All students

1.   Hartl, F.U. Protein folding. Secrets of a double-doughnut.  Nature, 371: 557-559, 1994.
(A scanned version of this paper, with attached color Fig. 1, is available on the Library ERes site)

2.   Lorimer, G. Protein folding. Folding with a two-stroke motor.  Nature, 388: 720-721, 1997.

• Individual assignments (Where two students are assigned to one paper: your choice as to how to divide. Student numbers are here)

3.   Braig, K., Otwinowski, Z., Hegde, R., Boisvert, D.C., Joachimiak, A., Horwich, A.L., and Sigler, P.B. The crystal structure of the bacterial chaperonin GroEL at 2.8 A.  Nature, 371: 578-586, 1994.
    Student #3: Figures 1, 2a & 3 ONLY. A scanned copy of this paper, with designated color figures attached, is available on the UAMS Library ERes site.

4.   Xu, Z., Horwich, A.L., and Sigler, P.B. The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex.  Nature,  388: 741-750, 1997.
    Students #2 & 8: Figures 1,2,5c & 6 ONLY.

5.   Chen, L.L. and Sigler, P.B. The crystal structure of a GroEL/peptide complex: Plasticity as a basis for substrate diversity.  Cell, 99: 757-768, 1999.
    Students #1 & 6: Figures 1 & 3, Table 1, and the text section on "Implications for binding..." (pp 765-766) ONLY.

6.   Chaudhry, C., Farr, G.W., Todd, M.J., Rye, H.S., Brunger, A.T., Adams, P.D., Horwich, A.L., and Sigler, P.B. Role of the gamma-phosphate of ATP in triggering protein folding by GroEL-GroES: function, structure and energetics.  EMBO J., 22: 4877-4887, 2003.
    Students #9 & 10: Figures 1,2,3, & 5D ONLY.

7.   Shtilerman, M., Lorimer, G.H., and Englander, S.W. Chaperonin function: Folding by forced unfolding.  Science, 284: 822-825, 1999.
    Student #4: Figures 1 & 2 ONLY.

8.   Lin, Z. and Rye, H.S. Expansion and Compression of a Protein Folding Intermediate by GroEL.  Molecular Cell, 16: 23-34, 2004.
    Student #5: Figure 7 and text section "Substrate protein confinement..." (pp 31-32) ONLY.

9.   Spiess, C., Meyer, A.S., Reissmann, S., and Frydman, J. Mechanism of the eukaryotic chaperonin: protein folding in the chamber of secrets.  Trends in Cell Biology, 14: 598-604, 2004.
    Student #7: Figures 1 & 3, and an overall summary; especially how the TRiC differs from GroEL/ES. (Much of the remainder remains speculative, so no need to elaborate on that)