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doi: 10.1242/10.1242/jcs.00256
Book Review |
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.
Institut für Organische Chemie und Biochemie, Technische Universität München, Garching, Germany
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.
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