Ear of Carrier Protein, 20th of June 2002
- 3-D structure determination -
You might not be the first person to be surprised at the strange title. However, "ear of protein" just means it has an ear-like part. We have already explained the carrier protein in cells. The protein that we will introduce to you this time is also one of the proteins to actively transport substances (of course including proteins) that are vital for life activities in cells. This protein is usually likened to Mickey Mouse because of the resemblance of its electron microscope picture. "Ear of protein" describes the part of ears in the scheme. Researchers call this part the "ear domain ".

Two main families of the carrier roteins The carrier proteins that we have already explained to capture the moment they take cargo are the family of proteins called GGA. The protein with ears is called the AP complex family corresponding to the GGA family. All of the AP complex family have ear domains and is thought to consist of 4 families generally (Figure 2). The 3-D structure of the ear domain of one of them, which is called the gamma subunit of AP1 complex involved in intracellular protein transport in human, has been determined for the first time in the world by the Structural Biology Group of Professor Soichi Wakatsuki as the research leader. The results of this research will appear in the July issue of Nature Structural Biology, a science magazine.
AP complex family has a variety of ears
The human's ear has the specific structure to be effective for listening sounds. In the same way, the ear domain of protein must have the specific structure for each function. Among the AP complex family, the research of AP2 complex has advanced because it was commonly found in neurons. In general, the domain structures of proteins are as follows:
1. Alpha helix, which amino acids that make up the domain are spiral
2. Beta sheet, which is plain-like and with many folding
3. Short parts such as random coils without repeating structure joined together to linear and then folded to form a 3-D structure.
Figure 3 shows this domain structure. It shows that the gamma ear domain of the AP1 complex determined this time is considerably different from alpha or beta ear domains of the AP2 complex. Important results for investigating the mechanism of these carrier proteins when they perform the transport function have been obtained, such as that the gamma subunit of the AP1 complex is comprised of only a beta sheet like the plane tape that gets tangled, is lacking the pocket-like structure to bind to external proteins which the alpha ear domain of AP2 complex has, and so on.

Comprehension of the function of GGA family is also advancing

The GGA family, which acts in the same transporting pathway as the AP complex family, also has a similar domain with the one discovered this time and the amino acid sequence that makes up this domain. For this, these research results are of great help in estimating the structure of the GGA family protein. As a result, it is thought that the structure of the second domain may be almost clarified, following the first domain called VHS of GGA protein (Figure 4) that the structure has been determined as explained last time.

The importance of the 3-D structural research of protein

Intracellular substance transportation is a vital function to support life activities in cells. It is well known that abnormalities of proteins involved in intracellular transport and subsequent protein transport to wrong sites cause a number of diseases. For example, abnormality of intracellular transport in neurons, in which intracellular transportation of transmitter substances is actively performed, may lead to neuroparalysis. Research to understand the function and the structure of proteins involved in intracellular transport is a crucial task for both basic biology and medicine. The determinations of 3-D structures of proteins among the materials structure science research of KEK show great promise.


Figure1
This is a scheme of protein transport pathway in a cell. Many transport pathways interlace between organelles, mainly endosome and trans-Golgi network.
High magnification (37 KB)


Figure 2

A scheme of 4 families of AP complex (AP-1?AP-4. AP complex is composed of 4 different kinds of subunits. In this research, the structure of the ear-like part (ear domain), which is sticking out, of the gamma subunit of AP-1 has been clarified.
High magnification (19 KB)

Figure 3
Left: The structure of the ear domain of the AP-2 alpha subunit (corresponding to left ear of AP-2 in Figure 2, red). Center: The structure of the ear domain of the AP-2 beta2 subunit (right ear of AP-2 in Figure 2:pink). Right: The structure of ear domain of the AP-2 gamma subunit that was determined in this research (corresponding to left ear of AP-1 in Figure 2, blue). The outlines of these 3 subunits are quite different, while the parts of structure shown in yellow are very similar.
High magnification (49 KB)


Figure 4

This figure exhibits the interaction between GGA1 protein and the other protein involved in the transport. GGA1 proteins are composed of 3 domain parts (as shown in the gray box). In the present study, the ear domain of the gamma subunit of the AP complex family, which acts in the same transport pathway in cells as GGA1, has been clarified. There are domains that have very similar amino acids sequences to this gamma subunit in the GGA family and the tertiary structures (GAE, indicated by pink circle) are also thought to be similar to the gamma subunit.
High magnification (54 KB)

Related articles
1) Carrier Protein in Cells
2) Investigating Proteins b X-ray

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