edited by Peter Lund
 Oxford University Press (2001) 281 pages. ISBN 0-19-963868-3 £32.50

Molecular chaperones are everywhere in the cell — topologically and functionally. There are huge quantities of them in the cytosol and in almost every cellular compartment. Surprisingly, even in the absence of any stress they amount to a large fraction of the total cellular protein. Furthermore, many are essential proteins. Because these proteins are intimately involved in the formation and maintenance of protein structure in the cell, they are of key importance for a large variety of cellular processes ranging from signal transduction to transport-vesicle uncoating. Their discovery was accidential; nobody was looking for cellular machinery for protein folding, mainly because Christian Anfinsen's classical in vitro experiments had convincingly shown that protein folding was a spontaneous process governed by side-chain interactions of a given amino acid sequence (Anfinsen, 1973). It should be noted that Anfinsen also proposed that spontaneous folding may be modified by extrinsic factors. However, this prophetic statement did not stimulate research immediately. From the early cell biology experiments that led to the identification of many of the chaperone proteins, the field went on to study these proteins in splendid isolation in the test tube. Biochemistry and biophysics proved to be very powerful in elucidating how these intricate machines work, why and how they hydrolyse ATP, how their substrates (unfolded proteins) are recognized and what their three-dimensional structures are. It is becoming increasingly clear that molecular chaperones are multi-component molecular machines that perform large-scale domain movements as a consequence of ATP hydrolysis (Walter and Buchner, 2002). These somehow direct the conformation of the target protein.

Despite this progress in analysing the molecular mechanisms of assisted protein-folding, a clear picture of their in vivo function is still lacking. This is partly because there seems to be redundancy in their function, at least as determined by in vitro assays, and partly because they seem to engage in functional networks. Above all, their substrates, the folding intermediates, are short-lived and hard to isolate.

In the past decade, progress in analysing molecular chaperones has been rapid. Peter Lund's book is timely because we are beginning to see a rough `landscape' of the chaperone machinery of the cell. The Editor has made an excellent choice in both the topics covered and the authors. The 11 chapters have been written by leading experts in the field. They summarize state-of-the-art research in a number of different areas and provide a perspective of the issues to be resolved. Together they create a comprehensive picture of this field. The articles contain a wealth of information both on mechanistic details and on the broader connection between chaperones and a variety of cellular processes. The contexts in which chaperones are discussed, such as protein translocation, protein folding in organelles, signal transduction or protein degradation, highlight their promiscuous character concerning both their `substrates' and their contribution to seemingly different cellular processes. The complexity of the chaperone networks in the cell is best exemplified by the Hsp70 chaperones. Many isoforms of Hsp70 are present in the cytosol of both prokaryotes and eukaryotes. In addition, a large number of cofactors that regulate the activities of specific Hsp70 members have been identified. A further level of complexity is introduced by the functional cooperation with other chaperone systems. Accordingly, several articles in the book deal with this ubiquitous chaperone family, describing their contribution to fundamental cellular processes.

The book lives up to its title of discussing the role of `Molecular chaperones in the cell', although some authors seem to have had problems staying on course. However, the fact that not all of the authors maintained their focus on the in vivo issues is one of the strengths of the book, and reflects adequately a field in which the cell biologists and biochemists have been working fruitfully together guided by their favourite chaperones. The book is, and will remain for the next years, a valuable source of information for anybody interested in the cell biology of molecular chaperones.

References

Anfinsen, C. B. (
1973
). Principles that govern the folding of polypeptide chains.
Science
181
,
223
-230.
Walter, S. and Buchner, J. (
2002
). Molecular chaperones — cellular machines for protein folding.
Angewandte Chemie Int.
41
,
1098
-1113.