The role of metal ions in protein folding and structure is a critical topic to a range of scientists in numerous fields, particularly those working in structural biology and bioinorganic chemistry, those studying protein folding and disease, and those involved in the molecular and cellular aspects of metals in biological systems. Protein Folding and Metal Ions: Mechanisms, Biology and Disease presents the contributions of a cadre of international experts who offer a comprehensive exploration of this timely subject at the forefront of current research.
Divided into four sections, this volume:
- Provides case study examples of protein folding and stability studies in particular systems or proteins that comprise different metal ions of co-factors
- Reviews the proteins that shuttle metal ions in the cell to a particular target metalloprotein
- Illustrates how metal binding can be connected to pathological protein conformations in unrelated diseases, from cancer to protein deposition disorders such as Parkinson’s disease
- Addresses protein redesign of metal-containing proteins by computational methods, folding simulation studies, and work on model peptides — dissecting the relative energetic contribution of metals sites to protein folding and stability
Together, the 13 chapters in this text cogently describe the state of the science today, illuminate current challenges, propose future possibilities, and encourage further study in this area that offers much promise especially with regard to novel approaches to the treatment of some of the most challenging and tragic diseases.
Table of Contents
FOLDING AND STABILITY OF METALLOPROTEINS : Metal Ions, Protein Folding, and Conformational States: An Introduction. The Folding Mechanism of c-Type Cytochromes. The Mechanism of Cytochrome c Folding: Early Events and Kinetic Intermediates. Stability and Folding of Copper-Binding Proteins. Iron-Sulfur Clusters, Protein Folds, and Ferredoxin Stability. Folding and Stability of Myoglobins and Hemoglobins. MECHANISMS OF METAL TRANSPORTERS, AND ASSEMBLY: Frataxin: An Unusual Metal-Binding Protein in Search of a Function. Mechanism of Human Copper Transporter Wilson’s Disease Protein. METAL IONS, PROTEIN CONFORMATION, AND DISEASE: α-Synuclein and Metals.
Zinc and Misfolding. The Octarepeat Domain of the Prion Protein and Its Role in Metal Ion Coordination and Disease. METALLOPROTEIN DESIGN, SIMULATION, AND MODELS: Metallopeptides as Tools to Understand Metalloprotein Folding and Stability. The Folding Landscapes of Metalloproteins.
Cláudio M. Gomes is group leader at the Instituto Tecnologia Química e Biológica, a research institute affiliated with the Universidade Nova de Lisboa, Oeiras, Portugal. Born in 1970, Cláudio earned his PhD from the Instituto Tecnologia Química e Biológica in 1999, as a Gulbenkian PhD program in biology and medicine graduate. From 2000 onward, he gradually switched his research interests from bioenergetics and metalloprotein structure-function toward protein folding and structural biophysics of misfolding diseases. Until setting up his independent laboratory in 2003, he was assistant professor at the Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, where he started teaching in 2000. Cláudio has published more than 70 peer-reviewed papers.
Pernilla Wittung-Stafshede has been a professor in biological chemistry in the Chemistry Department at Umeå University, Umeå, Sweden since 2008. Born in 1968, she earned a PhD in physical chemistry from Chalmers University, Gothenburg, Sweden, in 1996. During 1997–1998, she did a postdoctoral period at Caltech, Pasadena, California. In 1999 she began her independent research career, with a focus on the role of metals in protein folding, as a chemistry professor at Tulane University, New Orleans, Louisiana. After 5 years at Tulane, she moved to Rice University, Houston, Texas in 2004 and became a professor in biochemistry. Pernilla has graduated 10 PhD students to date, has obtained several awards, and has published over 150 peer-reviewed papers.