|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
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.
This is a scheme of protein transport pathway in a cell.
Many transport pathways interlace between organelles, mainly
endosome and trans-Golgi network.
magnification (37 KB)
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.
magnification (19 KB)
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.
magnification (49 KB)
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.
magnification (54 KB)