|We have already
introduced research on the structure and the function of intracellular
carrier proteins several times. Genetic information recorded
to human genes producing proteins have almost been clarified
in the Human Genome Project under international cooperation.
The next important step is to find out about the structure
and the function of proteins made from the genetic information.
For this, the elucidation of vital phenomenon will advance
and it will become possible to find effective means of treating
diseases. In the U.S.A. or Europe, national projects of protein
research have started following the Human Genome Project.
In Japan, the national project "Protein 3000 Project",
in which KEK is participating, was launched this summer. Today,
we will introduce KEK's plan.
Protein 3000 Project
The purpose of this project is to analyze the structure and
function of 3000 or more kinds of proteins for 5 years. It
is thought that the analysis of about 10,000 kinds of proteins
is necessary to learn the basic structure and function of
proteins. This project aims to analyze more than a third of
the requirement, to obtain the rights by patenting, and to
develop the drugs through making full use of genetic information
The organizations at the core for the project are Riken Institute
of Physical and Chemical Research (Riken), High Energy Accelerator
Research Organization (KEK, PF), Hokkaido University, The
University of Tokyo, Yokohama City University, Kyoto University,
Osaka University, as shown in Figure 1.
There are 2 programs that pursue the analysis. One is the
comprehensive structural and functional analysis of the basic
structure of 2500 or more kinds of proteins using a large
scale and rapid method proceeded by RIKEN as the leader. The
other consists of individual programs to handle a total 500
kinds of proteins through the structural and functional analysis
according to 7 themes, focusing on the variety of the structure
and function of protein, with other institutes as leaders.
Here, we will explain the structural and functional analysis
of protein, one of the individual programs, performed by Professor
Soichi Wakatsuki's group in the Institute of Materials Structure
Science that has KEK as the leader. The researchers state
that the most noteworthy themes in this project are the intracellular
transportation and posttranslational modification (Figure
2). Both are vital roles that proteins play to maintain our
What is intracellular transportation?
As described before, proteins that are essential for maintaining
the life activities within the cells of which our bodies are
comprised, are transported to cell membranes or a destination
outside cells through the organelles in cells. Substances
as a transport signal are put on the protein and transported
as cargo for accurate transportation to the destination. There
are many hereditary diseases caused by the lack of normal
structure or function of the protein that regulates such transportation.
Accurate supply of protein to necessary places in the body
is indispensable for life activities. Thus, understanding
the function of carrier protein is crucial research in aspects
of both basic biology and medicine.
What is post-translational modification?
Some people might be unfamiliar with this specific term.
Proteins are made from genetic information recorded in genes
and the production of specific protein from the information
starts from reading out the sequence of amino acids, which
is the material of protein. The process by which an amino
acid sequence is read out from genetic information recorded
to the gene, and protein is created, is called translation.
An expression marked on gene information is translated and
is changed into an expression written in amino acid. Proteins
are created after this translation but it is not sufficient.
Post-translational protein is still immature so that it prepares
accessories for the job to become full-fledged and start to
act (Figure 3). This process is called modification. Modification
means decoration or restriction. Modification of protein indicates
that protein is equipped with the material and tools to play
a limited role. The protein of KEK's research, which is the
structural and functional analysis of protein on the theme
of post-translational modification, is equipped with sugar
chains. Sugar chains are substances that sugar, such as glucose
or fructose, links together to form a chain. Sugar chains
on the surface of proteins confer important roles, such as
the "label," which indicates the type of protein,
"connector," which joints proteins to each other,
and "sign," which helps to distinguish the type
of cell, on proteins. Since most proteins exert their functions
when they are equipped with sugar chains, the elucidation
of the structure and the function of the sugar chains bound
to protein are critical themes in protein research.
Proteins equipped with sugar chains also closely relate to
intracellular protein transport. The analysis that both research
fields are mutually complemented is expected to develop rapidly
in these research fields. As introduced before, the synchrotron
radiation facility in KEK has shown great activity in performing
the X-ray structural analysis of protein. We plan to use this
facility for the program "Protein 3000 Project"
and the researchers who jointly use this facility will also
participate in this program (Figures 1 and 4). We will continue
to introduce this program targeted to carry out the structural
and functional analysis of 70 kinds of proteins in the next
5 years, according to the results that will be obtained.
Protein 3000 Project is the national project that aims to
promote research such as the structural and functional analysis
of approximately 3000 or more kinds of proteins and patenting
the results obtained in the 5 years from FY 2000. The project
is generally divided into the comprehensive analysis program
(by RIKEN) and the individual analysis program (by institutes
such as universities). The former will carry out the structural
and functional analysis of 2500 kinds of proteins and the
latter 500 kinds.
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Organizations that participate Protein 3000 Project
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Among the individual programs, the Structural Biology Group
of KEK, PF was selected as the core institute for the research
themes such as the posttranslational modification and transport.
The group will perform the structural and functional analysis
of proteins involved in these research themes, collaborating
with other research institutes.
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Proteins after translations from genes are still immature
and need various modifications such as the glycosylation before
they obtain their finished form. Moreover, in the process,
proteins need to be transported to various intracellular organelles
or outside the cells by intracellular transport. Thus, posttranslational
modification and intracellular are closely related to each
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This is an example of technology development by the Structural
Biology Group of KEK, PF as a leader aiming at high utilization
and convenience of the researchers who jointly use the facility.
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