Protein interactions in the context of folding, misfolding \& aggregation
Seminar Room 1, Newton Institute
Protein folding is perhaps the most fundamental process associated with the generation of functional structures in biology. There has been considerable progress in the last few years in understanding the underlying principles and dominant interactions that govern this highly complex process. Recently, much research has also focused on the realisation that proteins can misfold in vivo and that this phenomenon is linked with a wide range of highly debilitating diseases that are becoming increasingly prevalent in the modern world. We have been investigating in particular the nature of the amyloidogenic conditions, that include Alzheimer's disease, type 2 diabetes and the spongiform encephalopathies, e.g. BSE and CJD, in which protein misfolding leads to the aggregation of proteins, often into thread-like amyloid structures. Our studies have led us to put forward new ideas concerning the fundamental origins of the various diseases associated with their formation and the various strategies that can be used for their prevention and treatment. We have also speculated more generally that the need to avoid aggregation could be a significant driving force in the evolution of protein sequences and structures.
M. Vendruscolo, J. Zurdo, C.E. MacPhee and C.M. Dobson, Protein Folding and Misfolding: A Paradigm of Self-Assembly and Regulation in Complex Biological Systems, Phil. Trans. R. Soc. Lond. A 361, 1205-1222 (2003).
M. Dumoulin, A.M. Last, A. Desmyter, K. Decanniere, D. Canet, G. Larsson, A. Spencer, D.B. Archer, J. Sasse, S. Muyldermans, L. Wyns, C. Redfield, A. Matagne, C.V. Robinson and C.M. Dobson, A Camelid Antibody Fragment Inhibits the Formation of Amyloid Fibrils by Human Lysozyme, Nature 424, 783-788 (2003).
F. Chiti, M. Stefani, N. Taddei, G. Ramponi and C.M. Dobson, Rationalisation of Mutational Effects on Protein Aggregation Rates Using Simple Physical Principles, Nature 424, 805-808 (2003).
C.M. Dobson, Protein Folding and Misfolding, Nature 426, 884-890 (2003).
C.M. Dobson, In the Footsteps of Alchemists, Science 304, 1259-1262 (2004).