Protein Movers and Shakers
Protein Folding and Metal Ions: Mechanisms, Biology and Disease Edited by Cl udio M. Gomes and Pernilla Wittung-Stafshede. CRC Press, Boca Raton 2010, XIV + 294 pp., hardcover $ 149.95.—ISBN 978-1-4398-0964-8
Metals are essential to life and play a critical role in protein structure and function. In the last decade, the importance of metal ions in proteins has been an attractive research subject for the community engaged in studying protein folding stability and mechanisms. This book collects and summarizes previous results and findings from studies on the roles of metal ions in protein folding. There are 13 chapters in the book, which is divided into four sections. Section I, “Folding and Stability of Metalloproteins” (Chapters 1 to 6) reviews work on the effects of metal ions on the folding of several metalloproteins, such as heme proteins (c-type cytochromes, hemoglobin, myoglobin), copper-binding proteins (azurin, Atox1, ceruloplasmin), and iron– sulfur proteins (ferredoxin). Section II “Mechanisms of Metal Transporters and Assembly”, comprising Chapters 7 and 8, discusses the assembly and metal-transporting control of frataxin and Wilson’s disease (WD) protein. Section III, “Metal Ions, Protein Conformation, and Disease”, covers Chapters 9 to 11 and summarizes the roles of metal ions in several diseaseassociated proteins including a-synuclein, p53, and the prion protein (PrP). Section IV, “Metalloprotein Design, Simulation, and Models” (Chapters 12 and 13) discusses the design and folding landscapes of metalloproteins through a combination of experimental and theoretical approaches. Both editors of the book are experts in this field, and they have organized the sections and chapters in a relatively nice way for readers to understand the conChemBioChem 2011, 12, 647 – 649
tributions of metal ions in metalloprotein structures and folding mechanisms. The case studies discussed in Section I provide detailed information for readers to gain the knowledge and key points about protein folding and metal ions. Even readers who are not familiar with this field can understand the fundamental issues and problems relating to the roles metals play in proteins. A variety of biophysical techniques are also described in Section I, thus giving new researchers interested in this field a very good introduction. Moreover, Chapter 6 reviews comprehensive studies on the folding of myoglobins and hemoglobins, and describes a very detailed analysis of this. In particular, the complete derivations and expressions that explain the mechanisms are included in the appendix. Readers should find these equations very helpful and useful in understanding the experimental approaches and results. This could be the most impressive part for me, since I have not seen such detailed derivations in other books. Although only two examples, frataxin and WD protein, are discussed in Section II, the content presents a nice overview of the functions and structures of these two proteins and their metal-regulation mechanisms. In contrast to the folding studies in Section I, Section II gives readers another view of the relationship between metals and protein functions. The misfolding of a-synuclein and the prion protein is associated with neurodegenerative diseases, and loss of p53 function is associated with many forms of cancer. The three chapters in Section III discuss the interactions between metals and each of these proteins. The experimental observations and discussion presented in this section offer valuable information for readers to learn the contributions of metal ions to the process and consequences of protein misfolding. In the last section of the book, Chapter 12 describes the design of metalloproteins
from basic concept to practical approach. Essentially, the noncovalent interactions in proteins are the key to protein design, and this chapter provides such information and a few studies on designed metallopeptide models. The chapter also discusses the use of these designed metallopeptides to mimic metalloproteins and study their folding. Chapter 13 is the only chapter in the book to cover theoretical studies of the folding landscapes of metalloproteins. It has been always a difficult task to employ theoretical approaches in studying the folding of metalloproteins due to the involvement of metal ions. In this chapter, theoretical and simulated studies of cytochrome c and azurin folding are presented, and the calculated results are compared to experimental data. These studies provide some successful examples that help readers to understand the folding landscapes of metalloproteins through theoretical approaches. One thing worth mentioning is that in most chapters there is an independent section at the end of the main text describing the future perspective; this provides researchers interested in this field with some hints for further studies. The major drawback I find with the book is that all the pictures are in black and white, thus making it somewhat difficult for readers to clearly see the protein structures and the metal binding sites. Other than that, the book provides a nice introduction to the field of protein folding and metal ions for first-time readers, and an excellent review for readers whose research work is highly involved in metalloproteins. Jia-Cherng Horng National Tsing Hua University (Taiwan) DOI: 10.1002/cbic.201100017
2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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