Carrier Protein in Cells, 21st of February 2002
-Capturing the moment of taking cargo-
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
Clathrin
Transporter protein receptor
Trans-Golgi Network membrane
Lumen
Cargo protein

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 thing.
Download the PDF file of the picture for a stereo-vision.

.

Figure 1-1
aaaaaaaaaaaaaaaaaaaaa
High magnification (47 KB)



Figure 1-2
****************
High magnification (47 KB)




Figure 2
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.
High magnification (40 KB)




Figure 3
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 other.
High magnification (27 KB)





Figure 4
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.
High magnification (56 KB)

Related articles
Investigating Proteins by X-ray -Synchrotron radiation will open the way for structural biology-

Please send comments on the content of this Web site to:
Public Relations Office
proffice@kek.jp