|The human body
is made up of no less than 60 trillion cells. Each single
cell is maintained by unique actions of proteins, which enable
life. For that reason, investigating what kind of protein
structure generates its actions in cells is an important
theme in life science, especially medicine and pharmacology.
This also leads to the development of proteins and drugs
that benefit our lives.
Today's topic is the structural and functional research
on the carrier protein in cells clarified by Professor
Soichi Wakatsuki, the research leader. This topic was published
in today's issue of Nature. The protein featured in Nature
is called GGA1. In this article, the authors fixed GGA1,
a carrier protein in cells, as crystals at the moment of
its checking the label that was put on a cargo protein
and solved its crystal structure using strong lights (the
synchrotron radiation) from the accelerator. As a result,
they linked the function of this carrier protein to its
structure. Proteins are considered the machines living
molecules. The mechanism by which the carrier protein confirms
the cargo protein has finally begun to be understood.
Why is the role of carrier protein in cells so important?
In cells, there are many tiny organelles taking charge
of the primary activity of cells. You may be aware of the
nucleus in charge of managing gene information, or mitochondria’s
working to produce the energy used in cells. The activity
of these organelles requires constant transport of substances.
In other words, the transportation of substances in a cell
supports the activity of the cell. The investigation of
the roles of carrier proteins that control the substance
transport in cells is the basic research of life science,
which aims to understand cell activity. It will also open
up new opportunities for applications in medicine.
The article published by Nature this time explains the
action from the structure through grasping the moment that
GGA1 confirms the cargo. The authors have perfectly captured
how the carrier protein, using its tentacle-like part,
identifies the label that the cargo protein temptingly
puts outside the membrane of the small organelle, which
produces the cargo protein itself. The relation between
the carrier protein and the label is like "a ball
and a catcher's mitt", with electrostatic surface
potential or with selecting the region that hydrophobic
and hydrophilic parts contact.
If carrier proteins act incorrectly, disease such as cardiac
enlargement may be caused. The results of this research
will lead to the development of new drugs.
The research to understand the function of protein supporting
our life activity through investigating its three-dimensional
structure using the light created by the accelerator is
also an important activity of KEK.
Domain structure of GGA1 proteins
Transporter protein receptor
Trans-Golgi Network membrane
This figure exhibits the interaction between GGA1 protein
and the other protein involved in the transportation. GGA1
proteins are composed of 3 domain parts (as shown in the
gray box). The 3-D structure of the region where the VHS
domain of GGA1 protein (carrier protein) interacts with
the transporter protein receptor ("label") located
at the membrane has been demonstrated in the present study.
This is the structure of the carrier protein GGA1, which
has been clarified in the present study. “a” shows
GGA1 alone, “b” shows that GGA1 binds to a
receptor protein at the interacting domain (corresponding
to "label" outlined by green line). “c” and “d”,
as well as “e” and “f”, are the
surfaces of the regions that GGA1 and receptor protein
recognize each other. You can see that “c” and “d” are
attracted and recognize each other by the electrostatic
surface potential (blue, positive; red, negative), and “e” and “f” by
both hydrophobic regions. (Modified from Shiba. T. et al.,
Nature vol. 415., pp.937-941., 2002)
The pictures above are for a stereo-vision of certain
complex of the GGA1-VHS domain and transporter protein
receptor. Use your left eye for the left picture, right
eye for the right picture and try to merge them together.
This will give you a 3-D view of the protein. If you don't
succeed, please print the PDF file and then do the same
Download the PDF file of the picture for a stereo-vision.
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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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