小園研究室Kozono Lab.

小園 晴生 准教授Haruo Kozono
小園研究室Kozono Lab.
研究分野Research Area
分子機能生物学Biophysics and Molecular Biology
研究テーマResearch theme


Haruo Kozono Associate Professor

Labo’s Website

Kozono Lab.
Research Category
Division of Biosignaling
Research theme
Structural fluctuation of proteins detected by X-ray single molecule analysis.
Brownian motions of peptide/MHC complexes that define the activation of T cells.
DM effects on the peptide exchange reaction.
Dynamic properties of diabetogenic MHC I-Ag7.

We are interested in the structural fluctuations in proteins and the relationship of these fluctuations with function. Since proteins are sequences of amino acids, it is conceivable that amino acid fluctuation may influence protein function. However, few methods are currently available for detection of protein behavior, and the existing methods have limitations. We have developed and used X-ray single molecule analysis methods that detect nanometer-scale motion of proteins at the single molecule level. T cell receptors recognize peptides bound to major histocompatibility complex (MHC) proteins. In the case of MHC class II proteins, the peptide is a part of the MHC protein from the standpoint of protein folding. The crystal structures of peptide/MHC complexes indicate that the peptide is more rigid than the MHC molecule. However, we recently showed in biological assays that at least 2 conformations of peptide/MHC complexes exist: one in which the peptide is strongly bound and the other in which the peptide is loosely bound. These 2 forms of peptide/MHC complex activate different sets of T cells. We are investigating the different structural isotypes of the 2 forms. We are currently determining whether the structure of the peptide/MHC complex is fluctuating. If so, we will then determine how complex fluctuation affects its half-life, recognition by the T cell receptor, and the selection or exchange of suitable peptides. We hope that the results of these studies will help design strategies to regulate autoimmunity.