Researcher Information

Tomohide Saio

Assistant Professor

Proteins, from shape to function

Department of Chemistry, Physical Chemistry


Resolving the molecular mechanism of chaperone-assisted protein folding, holding, and translocation.

FieldStructural biology, Phisical chemistry, Biochemistry, Molecular biology
KeywordNuclear magnetic resonance (NMR), Protein structure, Paramagnetic lanthanide probe, Protein folding, Protein dynamics

Introduction of Research

Proteins are synthesized by the ribosome as unfolded polypeptides that lack higher order of structure, and eventually folded into its native fold so that they can exert their functions. Given the exposed hydrophobic regions in the unfolded state, the newly-synthesized proteins experience high risk of aggregation due to non-specific intermolecular hydrophobic contact that cause severe aggregation and amyloid formation. To prevent the aggregation or amyloid formation and to accelerate the folding to the native state, a number of molecular chaperones are working in the cell (Fig. 1). Dysfunction of molecular chaperones may cause severe aggregation and/or amyloid formation, which is often related to the neurodegenerative diseases. Our study aims to unveil how the molecular chaperone mediates protein folding, holding, and translocation in the cell. We mainly exploit solution NMR that can investigate protein structure, dynamics, and interaction at atomic resolution.
We also focus on the development of the tools exploiting paramagnetic lanthanide ions for structural study of proteins. Paramagnetic lanthanide ions immobilized on a protein by site-specific lanthanide tags induce several types of paramagnetic effects that can be exploited to extract long-range structural information of the proteins (Fig. 2). With new methods, we aim to unveil new aspects of molecular chaperones and consequently unveil how the chaperones work to maintain proteostasis in the cell.

Fig. 1 Regularion of protein folding and activity by molecular chaperones.
Fig. 2 Paramagnetic lanthanide probe as a source of long-range structural information of the protein.

Representative Achievements

Oligomerization of a molecular chaperone modulates its activity.
Saio T, Kawagoe S, Ishimori K, Kalodimos CG.
Elife. 2018 May 1;7. pii: e35731.
Structural insight into proline cis/trans isomerization of unfolded proteins catalyzed by the trigger factor chaperone.
Kawagoe S, Nakagawa H, Kumeta H, Ishimori K, Saio T.
J Biol Chem. 2018 Sep 28;293(39):15095-15106.
Structural basis for the antifolding activity of a molecular chaperone.
Huang C, Rossi P, Saio T, Kalodimos CG.
Nature. 2016 Sep 8;537(7619):202-206. Epub 2016 Aug 8.
Ligand-driven conformational changes of MurD visualized by paramagnetic NMR.
Saio T, Ogura K, Kumeta H, Kobashigawa Y, Shimizu K, Yokochi M, Kodama K, Yamaguchi H, Tsujishita H, Inagaki F.
Sci Rep. 2015 Nov 19;5:16685.
Structural basis for protein antiaggregation activity of the trigger factor chaperone.
Saio T, Guan X, Rossi P, Economou A, Kalodimos CG.
Science. 2014 May 9;344(6184):1250494.

Related industries

Medicine, Functional food, Protein engineering
Academic degreePh.D.
Self Introduction

I'm focusing on molecular chaperones and try to unveil the mechanism. I enjoy cold winter in Hokkaido with skiing.

Academic background2002-2006 Under graduate studies in pharmaceutical sciences, Hokkaido University, Japan
2006-2008 Master of science, Graduate School of Life Science, Hokkaido University, Japan
2008-2011 Ph. D. student, Graduate School of Life Science, Hokkaido University, Japan
2011-2014 Postdoctoral associate, Chemistry & Chemical Biology, Rutgers University, U.S.A.
2014-2018 PRESTO researcher, JST
2014-present Assistant Professor, Division of Chemistry, Graduate School of Science
Affiliated academic societyProtein Science Society of Japan, The nuclear Magnetic Resonance Society of Japan, The Japanese Biochemical Society, The Biophysical Society of Japan, The Chemical Society of Japan
Room addressGeneral Research Building 7 2007-1-18