Molecular Biophysics I
2005
Session #9

Molecular Chaperone Networks:
Cooperation between Different Chaperone Families

March 30, 2005
ED 2, G110 A/B
1:00 p.m. - 3:50 p.m.

The life of a protein in vivo involves a series of sequential events (biosynthesis, folding, function, unfolding, degradation) each of which presents slightly different protein conformations to the cellular chaperone machinery. This may explain, at least in part, a need for different types of molecular chaperones in the cell. Thus, the question arises: "Of the many different molecular chaperones in the cell,  do specific chaperones (or chaperone machines) cooperate with one another in an integrative way?" That is, does each chaperone perform its functions at a discrete step (or steps) in the life of a protein, and then "hand-off" further responsibilities to other chaperones, better equipped to handle subsequent events?

The answer appears to be 'yes'; evidently the cell does not wish for non-native proteins to ever be without a chaperone!

"Over the past decade, the pendulum has swung from the norm being disbelief in molecular chaperones as important in protein maturation in vivo, toward a view that molecular chaperones are required for each and every step of the life of each and every protein."

J. L. Johnson and E. A. Craig
Cell 90: 201-204, 1997

In this session, we briefly consider several examples of cooperation between different chaperones, using as our reference sources several review articles (Refs. #1 through #4 below) and one new data paper (Ref. 5). The specific examples of cooperating chaperones are:

•  Ribosome-bound chaperones and cytosolic Hsp70;

•  Hsp70 and/or GimC and the chaperonins (GroEL/ES and TRiC);

•  Hsp70 and Hsp90;

•  The calreticulin/calnexin cycle in the ER;

•  Cooperation under conditions of cellular stress, specifically heat and oxidizing agents:

  •  The redox chaperone Hsp33: general properties;

  •  Hsp33 and the DnaK chaperone machine under conditions of cellular stress (heat + oxidizing agents):

    •  How and why the DnaK machine might be transiently inactivated.

Student Assignments: (see Student Roster) Review articles are often collections of factoids, and thus difficult to summarize further. Thus, where you can, concentrate on the figures indicated, and try to build a short synopsis from them.

•  Student #1: Hsp70 and Hsp90: Young et al, pp. 786-789 + Box 4 & Fig. 3;

•  Student #3: Ribosome-bound factors and Hsp70: Young et al, pp. 782-784 and Fig. 1;

•  Student #7: Hsp70 and/or GimC and the chaperonins (GroEL/ES and TRiC): Young et al, pp. 784-786 plus Fig. 2 & Box 3;

•  Student #5: Small Hsps: The Haslbeck paper (your choice of which (or all) Figs to discuss)

•  Student #6: The calreticulin / calnexin cycle: Helenius & Aebi, 2004: PP. 1028-1037, but especially Fig. 3;

•  Students #2, 4, 8, 9 & 10: Hsp33

  • Student #9: Summary of function of Hsp33: Winter & Jakob, pp. 298-303, especially Fig. 1;

  •  Student #8: Temperature-induced changes in GrpE: Winter & Jakob, pp. 310-312 and Fig. 6;

  •  Students #2, 4 & 10: Temperature-induced inactivation of DnaK;

    •  Student #2: Winter et al, 2005, Figs. 1 $ 2;

    •  Student #4: Winter et al, 2005, Figs. 3 & 4;

    •  Student #10: Winter et al, 2005, Fig. 5 and 'Discussion' section

Reference List
(Note: all refs should be available electronically through the "UAMS Library catalog")

  1.   Young,J.C., Agashe,V.R., Siegers,K., and Hartl,F.U. (2004). Pathways of chaperone-mediated protein folding in the cytosol. Nature Reviews Molecular Cell Biology 5, 781-791.

   2.   Helenius,A. and Aebi,M. (2004). Roles of N-linked glycans in the endoplasmic reticulum. Annu. Rev. Biochem. 73, 1019-1049.

   3.   Haslbeck,M. (2002). SHsps and their role in the chaperone network. Cellular & Molecular Life Sciences 59, 1649-1657.

   4.   Winter,J. and Jakob,U. (2004). Beyond transcription--new mechanisms for the regulation of molecular chaperones. Crit Rev. Biochem. Mol. Biol. 39, 297-317.

   5.   Winter,J., Linke,K., Jatzek,A., and Jakob,U. (2005). Severe oxidative stress causes inactivation of DnaK and activation of the redox-regulated chaperone Hsp33. Mol. Cell 17, 381-392.