SPring-8, the large synchrotron radiation facility

Release Date

19 Feb, 2007

     The research group of Japan Synchrotron Radiation Research Institute (JASRI), Japan Science and Technology Agency (JST) and Tokyo University of Science has discovered that Brownian motions of the antibody molecule is inhibited considerably by antigen-binding reactions, using dynamical single-molecule detection system with X-rays (Diffracted X-ray Tracking (DXT)) at RIKEN Structural Biology II Beamline BL44B2 of SPring-8, and they succeeded in observing molecular behaviors in antigen-antibody reaction, which is considered as playing an important role in immunity. In addition, they clarified that the stronger antigen-antibody interaction, the Brownian motion of the antibody molecule is inhibited more by antigen-binding reaction. This is the first result to be able to quantitatively determine the biomolecular interactions at single-molecule level.

     The research group of JASRI and JST has been studying and developing the DXT method which can observe the single-molecule motions in the real-time at picometer-level accuracy. On the other hand, other current single molecular detection methods using visible light wavelength can not observe such a high accuracy molecular dynamics. The conformational change or structural fluctuation of antibody is one of the candidates for the signals for B lymphocyte activate mechanism. It has long been debated whether conformational changes occur in the antibody upon antigen-binding, which are related to the signals for triggering of effectors function. But the dynamical structural information of the antibody was little known. Since they achieved the quantitative determination of the antibody structural dynamics with antigen-binding, understanding the relationship between the structural dynamics of antibody and the signal transduction of one will be strongly accelerated. On the other hand, such new quantification in biomolecular interactions from picometer-level structural fluctuations using high sensitive detection system can be applied to various biological systems. Additionally this method will widely advance scientific studies in biotechnology and medicine as an ultimate analytical method.

     This work was supported by CREST "Protein Structure and Functional Mechanisms - Toward Creation of Innovative Medicines, Diagnosis, and Material Production Based on Functional Mechanisms of Proteins -" (Research Supervisor: Dr. Tairo Oshima) from JST, and will be published online in Biochemical and Biophysical Research Communications.

Publication:
"Dynamical regulations of protein–ligand bindings at single molecular level"
Takuma Sagawa, Takachika Azuma and Yuji C. Sasaki
Biochemical and Biophysical Research Communications 355 (2007) 770–775, available online 15 February 2007