Picobiology : Life Science at the atomic level

Picobiology: Life Science at the atomic level" was selected in 2007 as one of the 13 programs in the field, "Life Science

Introduction of Picobiology Institute

The objective of this institute which is the center for the promotion of picobiology is for protein structural analyses at picometer level as given below. The protein is a chain molecule consisting of more than 100 molecules of 20 different types of amino acids. Different types of proteins have different amino acid sequences. The chain is folded in a fixed shape. The function of the protein (function that drives the chemical reaction, a life phenomenon) is driven by these amino acids.
The spacial distribution of these amino acids in the protein is determined by X-ray crystal structure analysis and the function is precisely analyzed by vibrational spectroscopy. The specific steps can be summarized as [1] crystallization of the protein, [2] determination of the spatial distribution of amino acids by X-ray crystal structure analysis, [3] labeling of only the amino acids subjected to study, and [4] measurement of vibrational spectra of labeled amino acids.

The necessity and inter-relationship of these steps are as follows. Since there are only 20 species of amino acids, large protein contains many amino acids of the same species. Since the protein is folded together, adjacent amino acids have very strong interaction and although the amino acid are of the same kind, the chemical reactivity changes in many ways due to the difference in adjacent amino acids in the protein. Consequently, in the analysis of the structure of the protein, it is necessary first to determine the distribution pattern of the amino acids in the protein (that is to say, in the vicinity of an amino acid, which kind of amino acids is distributed) by high-resolution X-ray crystal structure analysis. However, due to the thermal vibration of the protein, it is impossible to raise the precision of structure analysis up to the precision (picometer) possible to analyze the chemical reaction. For this reason, it is necessary to analyze with high precision the structure of the amino acid by infrared spectrometry. However, because the protein contains a large number of amino acids of the same kind, it is impossible to determine which amino acid is giving the infrared spectrum. This difficulty can be overcome by isotope labeling. By labeling with the stable isotope such as 13C and 15N, the infrared spectra of specific labeled amino acids can be determined.
Department Constitution
In order to systematically carry out picobiology, the following five departments have been established in the gPicobiology Instituteh.

Department of Protein Crystal Growth Mechanism

Professor (Concurrent), Shinya Yoshikawa

Associate Professor (Concurrent), Kazumasa Muramoto

Assistant Professor, Masao Mochizuki

Preparation of crystal possible to be analyzed with X-ray structure analysis at 1.2 Å resolution (resolution possible to determine the position of hydrogen atom) and search of the crystallization conditions.

Department of Protein Structural Analysis

Professor, Tomitake Tsukihara

Assistant Professor (Concurrent), Shomura Yasuhito

Assistant Professor, Shin-ichi Terawaki

This department establishes experimental conditions to obtain high-resolution X-ray diffraction image possible of the protein crystal prepared by Department 1) and develop the X-ray structure analysis method. Also, the accessibility of SPring-8 beam lines nearby contributes to the promotion of research in this department.

Department of Site-Specific Isotope Labeling of Proteins

Professor, Hideo Shimada

Junior Associate Professor, Yukie Katayama

Assistant Professor, Ryota Aminaka

Development of the site-specific protein isotope labeling method using cell-free synthesis system

Department of Protein Vibrational Spectroscopy

Professor (Concurrent), Takashi Ogura

Associate Professor, Satoru Nakashima

Assistant Professor, Minoru Kubo

Development and improvement of time-resolved high-precision infrared spectrometry system and resonance Raman spectrometry system, and analysis of the protein function using these systems

Department of Theoretical Research for Protein Functions

Professor (Concurrent), Atsushi Oshiyama

Associate Professor, Yasuteru Shigeta

Assistant Professor, Katsumasa Kamiya

This department aims at forming a chemical description of the function of the protein based on the results from Department [2] and [4]. It is expected that new problems are found during the processes and hence, new projects are started in Department [1] to [4].
Characteristics of the Research in Our Institute
As mentioned above, the objective of picobiology is to describe life phenomena in chemical language.
However, there is a high possibility that description through a known chemical language only is not possible. At the functional center of the protein are various amino acids spatially distributed and is thought to have a structure impossible (very difficult) to create artificially outside of the protein. Chemical reactions occurring in the site with such a structure are assumed to have characteristics not studied thus far (not known) in the chemical field. For a description of such a chemical reaction (structure elucidation), a new chemical word needs to be created. Consequently, in our research center, a new research field is born (the boundary between biology and chemistry). A distinction should be made of this field from conventional gbiological chemistryh which studies the structure of cell components chemically (in existing chemical words) simply as one of the chemical substances. It is recommended that this is called gpicobiologyh.

For chemical reactions driven by the small simple proteins, it is thinkable there are many reactions that can be described sufficiently with existing chemical words; however, for establishing picobiology, (for pioneering a new field), the elucidation of life phenomena controlled by the highly organized protein system should be challenged. Accordingly, at our life science department, an immediate challenge is to study the function of the mitochondrial respiratory system centering on cytochrome c oxidase promoted powerfully thus far. The complexes comprising the respiratory system are large membrane protein complexes with molecular weight of 200,000 to 1 millions, and the functional centers are located deep inside the proteins. It can be anticipated that this complex has a protein system with a high possibility of carrying out a gchemical reactionh not describable by existing chemical words. Also, the mitochondrial respiratory system is a system for the synthesis of ATP indispensible for maintaining life and studying the system is one of the most important assignments of life science. Thus, this research subject is considered most appropriate one for developing this institute as a world-class life science research center.