General Models Of Chaperonin Action

We have attempted to summarize a body of knowledge on the kinetics and energetics of protein folding, on the functional properties of the chaperonins, and on the interplay between the two. The information available is by no means complete, but it is sufficient to suggest models of the molecular mechanism by which this energy-dependent process leads to an enhancement of folding efficiency. The types of model currently envisaged fall into three categories. None requires specificity in the...

Ligand Complexes Binary and Ternary

Substrates bound to GroEL are thought to be in a partially folded form, with native secondary structure, but with expanded and incomplete tertiary structure (the molten globule) (Goloubinoff et al, 1989 Martin et al, 1991 van der Vies et al., 1992). The position of substrate binding in the central channel in end projection was first suggested by negative stain EM of GroEL complexes with rhodanese and alcohol oxidase (Langer et al., 1992), and by scanning transmission EM of complexes with...

Spontaneous Protein Folding

The experimental model of assisted protein folding from which almost all physical data have been derived is based on unfolding the protein substrate by use of chaotropic d naturants, pH, or heat and introducing the denatured form into native solvent conditions in the presence of chaperonins. To gain an understanding of the influence of chaperonins in such conditions, it is essential to consider what is known of the spontaneous folding process. The least native-like states of proteins are...

Concluding Comments

It is ironic that studies initiated in the 1980s to understand the complexity of higher plant chloroplast Rubisco assembly (Barraclough and Ellis, 1980 Gatenby et al, 1981 Roy et al, 1982 Bloom et al, 1983 Hemming-sen and Ellis, 1986 Musgrove et al, 1987 Gatenby et al, 1988) should have crossed paths with studies on bacteriophage assembly (Georgo-poulos et al, 1973 Hendrix, 1979 Tilly et al, 1981), to contribute instead to the discovery and characterization of the chaperonin family of molecular...

Info

Inc. THE CHAPERONINS All rights of reproduction in any form reserved. overwhelmed by an invading microorganism, adaptive immunity is activated in the form of antibody and T lymphocytes. Although the adaptive system takes some time to reach its peak, it improves the efficiency of the innate response and has specific memory of prior infection with the same microbe. This memory means that the second time a particular infectious agent invades an animal the adaptive...

On Phagocytes

Surprisingly, not only are chaperonins important immunogens for the adaptive immune system, but they also act directly on innate phagocytes (see Fig. 1). For example, the Mycobacterium leprae cpn60.2 (also called 65-kDa antigen) induces cytokine secretion from a human monocyte line, according to the findings of Friedland et al. (1993). These workers carefully excluded bacterial lipopolysaccharide from the cpn60.2 preparation, which is important because lipopolysaccharide can activate monocytes....

Autoimmune Disease

The role of chaperonins in autoimmune disease is controversial. At one end of the spectrum is the argument that although infection immunization with chaperonin-containing organisms is universal, and healthy people have T cell responses to self-chaperonins, classical autoimmune disease is quite uncommon. So the presence of immune reactions to chaperonins may be incidental and unimportant. At the other end of the spectrum is the idea of molecular mimicry (Cohen and Young, 1991). The theory is...

Functions Of Chaperonins

Validity of in Vitro Experiments Most of this volume discusses recent observations and interpretations of the structure and functions of the chaperonins, but a summary of key points may be useful here to orient the reader new to this field. A distinction should be drawn between those experiments performed in vitro with either defined components or isolated organelles and crude cell-free extracts, and those performed in vivo, usually by genetic means. The former experiments greatly outnumber...

GroELGroES Complexes Hinge Rotations in GroEL

In the presence of nucleotide, a complex is formed between GroEL and GroES (Chandrasekhar et al, 1986). GroES binds tightly to one ring of GroEL after ATP hydrolysis, trapping ADP in the seven sites on that ring (Todd et al, 1994). Adenosine triphosphate binding by GroEL is cooperative, and this positive cooperativity is increased by GroES, suggesting that all seven sites in the opposite ring of GroEL act together. With each round of ATP hydrolysis, the GroES is released and rebinds. The...

Role Of Atp In Chaperonin Activity

One of the most intriguing aspects of the chaperonins is their ability to capture chemical energy derived from the magnesium-dependent hydrolysis of ATP and use this to improve the yield of otherwise inefficient folding reactions. The requirement for an energy input is, at least at first sight, difficult to understand. In muscle the free energy of ATP hydrolysis is used in the contraction of fibers, and in membrane ion pumps it is used to drive the translocation of ionic species against...

Arrangement Of Subunit Domains In Chaperonin 60 Oligomer

Low-Resolution Studies of Chaperonins by Electron Microscopy The distinctive structure of cpn60 was observed in the 1970s by negative stain EM. Two views, a round one with sevenfold symmetry and a rectangular or square one with four stripes of density, were reported by Hendrix (1979) and by Hohn et al. (1979), when GroEL was described as a factor required for bacteriophage assembly. Chloroplast cpn60 was shown to have similar structure (Pushkin et al., 1982), and a 3D model was proposed, but...

Other Hypotheses

It is possible that the immune preference for chaperonins is due to exposure early in life to environmental bacteria that share epitopes with mycobacterial chaperonins. It is difficult to see how this can be true, because there is a high frequency of responses to mycobacterial cpn60 in the cord blood of newborn infants who have not been exposed to environmental bacteria. Another possibility is that bacteria synthesize large amounts of chaperonins, particularly when they are stressed, and this...

References

Principles that govern the folding of protein chains. Science 181, 223-230. Badcoe, I. G., Smith, C. J., Wood, S., Halsall, D. J., Holbrook, J. J., Lund, P., and Clarke, A. R. 1991 . Binding of a chaperonin to the folding intermediates of lactate dehydrogenase. Biochemistry 30, 9195-9200. Braig, K., Otwinowski, Z., Hegde, R., Boisvert, D. C., Joachimiak, A., Horwich, A. L., and Sigler, P. B. 1994 . The crystal structure of the bacterial chaperonin GroEL at 2.8 A Nature...