SEMINAR

APPA and Protein Science in Asia

In this informal dinner talk I will give an overview of research activity in protein science in Asia and the role of APPA in helping to develop this.

Supersaturation-limited Phase Transitions of Proteins

Abstract
Although amyloid fibrils and amorphous aggregates are two types of aggregates formed by denatured proteins, their relationship remains unclear. We previously suggested that amyloid fibrils and amorphous aggregates are similar to the crystals and glasses of solutes, respectively, and supersaturation is required to form crystal-like amyloid fibrils (1). We used β2-microglobulin (β2m), a protein responsible for dialysis-related amyloidosis, to clarify the mechanism by which proteins form either amyloid fibrils or amorphous aggregates. We succeeded in direct heat measurements of the formation of amyloid fibrils using isothermal titration calorimeter (2). We also characterized the thermodynamics of amorphous aggregation at high salt conditions, enabling the comparison of protein folding, amyloid fibrillation and amorphous aggregation. On the basis of the NaCl concentration-dependent changes in end products, we suggest that the apparent complexities in aggregation are explained comprehensively by a competitive mechanism in which supersaturation-limited phase transitions compete with supersaturation-unlimited transitions (3). We address the critical roles of supersaturation-limited phase transitions in various processes of proteins.

References
1. Yoshimura Y, et al. (2012) Distinguishing crystal-like amyloid fibrils and glass-like amorphous aggregates from their kinetics of formation. Proceedings of the National Academy of Sciences, USA 109:14446-14451.
2. Ikenoue T, et al. (2014) Heat of supersaturation-limited amyloid burst directly monitored by isothermal titration calorimetry. P Natl Acad Sci USA 111:6654-6659.
3. Adachi M, So M, Sakurai K, Kardos J, Goto Y (2015) Supersaturation-limited and Unlimited Phase Transitions Compete to Produce the Pathway Complexity in Amyloid Fibrillation. J Biol Chem 290:18134-18145.

BIOGRAPHY

1982: D. Sci., Osaka Univ., Graduate School of Science, Biochemistry
1982 -1984: Research Assistant, School of Medicine, Institute for Enzyme Research, Tokushima University
1984-1989: Research Assistant, Faculty of Science, Department of Biology Osaka University
1986-1988: Research Fellow, University of California, Santa Cruz
1989-1998: Associate Professor, Faculty of Science, Department of Biology Osaka University
1998-present: Professor, Institute for Protein Research, Osaka University,

Services to the Scientific Community;
Protein Society, Exective Council, 2007-2011
Asian Pacific Protein Association, President: 2010-2011.
Biochim. Biphysica Acta, Proteins and Proteomics, Executive Editor, 2008-2013
Protein Science, Editorial Board, 2003-present
J. Biol. Chem., Editorial Board, 2010-present
Protein Science Society of Japan, Board member: 2000-2005, 2008-2011, 2013-present