分子細胞生物 I

生命科学科3年後期�
分子細胞生物�I
相同アミノ酸配列の比較解析
藤　博幸
関西学院大学理工学部生命医化学科
Outline
1.  イントロダクション
2.  膜タンパク質のトポロジー反転
3.  ケモカイン受容体
Evolu&onaryfateandfunc&onalconsequence
Gene A
Gene A'
duplication
Gene A
Non-processed
pseudogene A
Function A
Non-functionalization
(pseudogenization)
Gene A
Gene B
Neofunctionalization
Functions A + B
Gene A'
Subfunctionalization
Gene A''
Functions A' + A'' = A
Evolu&onaryfateandfunc&onalconsequence
Gene A
Gene A'
duplication
Gene A
Non-processed
pseudogene A
Function A
Non-functionalization
(pseudogenization)
Gene A
Gene B
Neofunctionalization
Functions A + B
Gene A'
Subfunctionalization
Gene A''
Functions A' + A'' = A
Evolu&onaryfateandfunc&onalconsequence
Gene A
Gene A'
duplication
!
Which amino acid sitesNon-processed
are related to !
pseudogene A
Gene A
the functional
divergence
?!
Non-functionalization
Function A
!
(pseudogenization)
Gene A
Gene B
Neofunctionalization
Functions A + B
Gene A'
Subfunctionalization
Gene A''
Functions A' + A'' = A
Classical Approach !
to identify the critical sites!
for functional divergence !
!
- Evolution of Prostaglandin D Synthase - !
2
Nagata, A., Suzuki, Y., Igarashi, M., Eguchi, N., Toh, H., Urade, Y.,Hayaishi, O.
Proc. Natl. Acad. Sci. USA 88, 4020-4024 (1991).
Igarashi, M., Nagata, A., Toh, H., Urade, Y., Hayaishi, O.
Proc. Natl. Acad. Sci. USA 89, 5376-5380 (1992).
PGD synthase
O
COOH
HO
COOH
O
O
OH
PGH2
OH
PGD2
PGD Synthase
about 190 a.a.
Amino Acid Sequence Database
Database
Searching
Lipocalins
mouse PGD synthase�
human neutrophil gelatinase-associated lipocalin�
Lipocalin Family!
Diverse family of secretory proteins involved !
分泌蛋白質から構成されるグループで、疎水性の低分子に結合し、その輸送に携わっている。
in binding and transport of small hydrophobic molecules
secretory tissue!
lipocalin!
Small hydrophobic !
molecules!
target cell!
PGD synthases
enzyme!
!
Lipocalins!
transporter!
= non-enzyme!
!
!
vertebrates!
from bacteria to eukaruyotes!
Which sites are involved in acquisition !
of the catalytic activity ?
!
PGD synthase is inactivated by treatment with
.
SH
X
SH-Modifier�
Cys residues may be involved in the catalytic
reaction of the enzyme.
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
Site-Directed Mutagenesis
Cys
Ala, Ser
Cys
S
S
Mutants showed the
activity comparable
to that of their parent
enzyme.
SH
Cys
Cys
Mutants lost the enzyme activity.
More systematic and automatic method !
to detect the critical sites!
for functional divergence!
Deep insight into evolution of protein function
Clue for design and/or alteration !
of protein function!
Substrate A
Substrate B
amino acid sequence alignment !
consisting of groups with different functions
0 40058-6
04 0585 2 05835
0
098
0
098
0
098
0
098
conservation!
5
5
5
5
5
0 -15 17 5 5 3 0 9454
0 015517 5 533 3
0 945
-3 15 17553333 0 464
515 1715 5 25
515 1715 5 25
515 1715 5 25
515 1715 5 25
0
098
56
515 1715
0
098 3 5
015 1715
0 93 983
550 16 1715
374 0
5 0057 17 5
74 5 03 -5 055 6 1715
574
3 5 055 5517 5
574
3
5 055 5517 5
5
5
55
5
5
65
65
25
25
574
33
5
574
3 5
574
3. 5
574
3 5
374 0 33 5
374 0 33 5
7
53 35
37
3 5
65
65
65
35
65
65
65
65
35
1
35
31
35
31
5
9312
35
1
35
1
35
35
7
-
055
055
055
0 5
055
055
055
55
5517
5517
5517
5517
5517
5517
5517
5 17
5
5
5
5
5
5
5
5
2
0- 434
3 77454
1237
35
7
35
1
amino acid composition
evolutionary rata!
Conservation
Evolutionary Trace
Quantitative Evolutionary Trace
Evolutionary Rate
Hierarchical Conservation Analysis
Diverge
Amino Acid Composition
Cumulative Relative Entropy
Relative Entropy among Paralogs
Level Entropy
Branch Length
Outline
1.  イントロダクション
2.  膜タンパク質のトポロジー反転
3.  ケモカイン受容体
Aquaporin
Fu et al.. Science 290, 481-486 (2000).
Murata et al.. Nature 407, 599-605 (2000).
ClC chloride ion channel
Dutzler et al. Nature 415, 287-294 (2002).
a b
N
c
a b c
C
・The N-terminal domain is homologous to the C-terminal domain.
・The arrangement of the two domains are opposite to each other.
Membrane proteins have bias in amino acid composition
at the membrane boundary. ex) positive inside rule
The amino acid composition of cytoplasmic proteins
is different from that of the extracellular proteins
extracellular
region
membrane
＋�
＋� ＋�
＋�
＋�
＋�
cytoplasmic
region
von Heijne, Nature, 341, 456-458 (1989)
Nakashima & Nishikawa FEBS Lett. 303,
141-146 (1992)
Nakashima & Nishikawa J. Mol. Biol. 238, 54-61 (1994)
a b
N
c
a b c
C
・The N-terminal domain is homologous to the C-terminal domain.
・The arrangement of the two domains are opposite to each other.
The two domains are expected to have evolved
under deferent constraints.
Different constraints are considered to have been working on
the interfaces against the extracellular and cytoplasmic environments.
Extracellular Region
Membrane
Pore Surface
Cytoplasmic Region
3. Methods
(1) Multiple Alignment
(a) Collection of homologous amino
acid sequences by database searching
Sequence DB
N-termnal domains C-terminal domains
(b) Cleavage of the obtained sequences
into the N- and the C-terminal domains
(c) Multiple alignment of each domain
(d) Profile alignment between the alignments
of the N- and the C-terminal domains
Evaluation of difference between two domains at each alignment site!
Amino acid residue frequency Ala Arg
at the alignment site i in the
0.05 0.03
chmokine receptor
Site 1 . . .
Site i . . .
Trp
0.01
Site L
Protein １
Protein ２
Protein ３
Protein M
chemokine
receptor
Protein １
Protein ２
Protein ３
Protein N
a cluster of
decoy or viral
receptor
Ala Arg
Amino acid residue frequency 0.02
at the alignment site i in the
a group of decoy or viral receptor
0.05
Trp
0.03
Estimation of Amino Acid Composition !
at Each Alignment Site
・Taxonomic Bias!
Henikoff & Henikoff weight!
・Unobserved Residue
Pseudocounts adopted !
in PSI-BLAST
※ it is the same method used for the calculation of PSSM in !
PSI-BLAST (β = 0.1)!
※ BLAST parameter λu was obtained by Newton-Laphson method !
at each calculation.!
※ CRE uses Dirichlet mixture as a prior instead of pseudocount.!
Evaluation of difference between two domains at each alignment site!
Amino acid residue frequency Ala Arg
at the alignment site i in the
0.05 0.03
chmokine receptor
Site 1 . . .
Site i . . .
Trp
0.01
Site L
Protein １
Protein ２
Protein ３
Protein M
chemokine
receptor
Protein １
Protein ２
Protein ３
Protein N
a cluster of
decoy or viral
Kulback-Leibler information
between the two groups
calculated at each alignment
site.
receptor
Ala Arg
Amino acid residue frequency 0.02
at the alignment site i in the
a group of decoy or viral receptor
0.05
Trp
0.03
The difference between two probability distributions can be !
quantitatively evaluated with Kullback-Leibler information (KLI).!
(１) Definition of KLI!
p(1)+p(2)+p(3)+ . . . +p(20)=1.0
20
Σ
p(i) log
i=1
p(i)
q(i)
(2) Asymmetry of KLI!
…
p(i)
20
Σ
p(i) log
i=1
q(i)
=
20
Σ
q(i) log
i=1
q(i)
p(i)
(3) Modified KLI used in this study.!
20
…
Σ
p(i) log
i=1
q(1)+q(2)+q(3)+ . . . +q(20)=1.0
p(i)
q(i)
+
20
Σ
q(i) log
i=1
q(i)
p(i)
Sites with top 5% KLI!
Different Constraints
Difference in Amino Acid Composition or Conservation Pattern
If an alignment site shows large difference
between the N- and the C-terminal domains,
the site is considered to have been
subject to different constraints between the domains.
(1)  How to evaluate the difference between two domains?
(2) How large difference is considered to be significant?
Two Problems for estimation of residue frequency
at each alignment site.
�
��
・Taxonomic Bias
Henikoff & Henikoff weight
・Unobserved residue
Pseudocount adopted in PSI-BLAST
※ BLASTparameterλis obtained by Newton-Laphson method at each calculation.
※ As the background compostion of amino acid residues, the compostion obtained
from database analysis, and the one obtained from the multiple alignment under
consideration were examined. However, no significant difference was observed.
・Number of Sequences used for the analysis
aquaporin family
50 sequences (The alignment consists of 100 sequences)
ClC chloride channel family 50 sequences (The alignment consists of 100 sequences）
・The distribution of the KL information follows Γ distribution.
30
60
25
50
20
40
系列1
15
系列2
10
20
5
10
0
0
-1.5 1 -1.02 -0.53 0.0 4 0.5 5 1.0 61.5 7 2.0 8 2.5 9 3.0 103.5 11
*
aquaprorin family
系列1
30
系列2
-2.01 -1.52 -1.03 -0.54 0.05 0.56 1.0 7 1.5 8 2.0 9 2.510 3.011 3.512
*
ClC chloride channel family
χ2 = 4.176
χ2(6, 0.01) =16.819
χ2 = 5.625
χ2(7, 0.01) =18.473
Oberved frq.
Expected frq.
4. Results & Discussion
The residues of 1J4N and the amino acid compositions corresponding to the sites selected from the alignment of aquaporins
N (S28)
C (V155)
A
R
N
D
C
Q
E
G
H
I
L
K
M
F
P
S
T
W
Y
V
0.07 0.00 0.00 0.00 0.00 0.00 0.00 0.64 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.10 0.19 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.39 0.14 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.47
N (F58)
C (I174)
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.05 0.14 0.00 0.00 0.00 0.00 0.53 0.00 0.00 0.00 0.28 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.65 0.00 0.00 0.00 0.07 0.06 0.00 0.00 0.00 0.00 0.22
N (H76)
C (G192)
0.05 0.00 0.05 0.00 0.00 0.00 0.00 0.00 0.90 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.20 0.00 0.00 0.00 0.05 0.00 0.00 0.21 0.00 0.00 0.00 0.00 0.00 0.00 0.17 0.37 0.00 0.00 0.00 0.00
N (V81)
C (R197)
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.02 0.03 0.00 0.05 0.05 0.00 0.00 0.00 0.00 0.00 0.86
0.00 0.95 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.05
N (L85)
C (S201)
0.07 0.00 0.00 0.00 0.02 0.00 0.00 0.00 0.00 0.00 0.49 0.00 0.14 0.19 0.00 0.00 0.00 0.00 0.05 0.04
0.14 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.78 0.05 0.00 0.00 0.00 0.03
N (I97)
C (W212)
0.02 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.25 0.22 0.00 0.00 0.06 0.23 0.00 0.00 0.00 0.00 0.22
0.00 0.04 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.02 0.06 0.00 0.00 0.00 0.04 0.00 0.00 0.83 0.00 0.00
N (Q103)
C (P218)
0.00 0.00 0.00 0.00 0.00 1.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.97 0.00 0.03 0.00 0.00 0.00
N (L114)
C (Y229)
0.11 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.03 0.45 0.00 0.03 0.03 0.00 0.00 0.05 0.00 0.00 0.31
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.15 0.03 0.00 0.05 0.00 0.00 0.00 0.00 0.00 0.04 0.73 0.00
The residues of 1J4N and the amino acid compositions corresponding to the sites selected from the alignment of ClC chloride ion channels
N (R147)
C (I356)
A
R
N
D
C
Q
E
G
H
I
L
K
M
F
P
S
T
W
Y
V
0.03 0.38 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.03 0.52 0.00 0.00 0.04 0.00 0.00 0.00 0.00 0.00
0.06 0.00 0.00 0.00 0.00 0.03 0.04 0.02 0.00 0.27 0.23 0.00 0.03 0.00 0.00 0.00 0.00 0.00 0.06 0.27
N (E148)
C (F357)
0.00 0.03 0.00 0.00 0.00 0.00 0.91 0.00 0.00 0.00 0.00 0.00 0.04 0.00 0.00 0.00 0.00 0.00 0.00 0.02
0.00 0.00 0.02 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.03 0.00 0.00 0.83 0.00 0.00 0.00 0.00 0.05 0.07
N (Q153)
C (A362)
0.00 0.00 0.00 0.00 0.00 0.36 0.04 0.00 0.55 0.00 0.02 0.00 0.03 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.24 0.00 0.05 0.00 0.00 0.00 0.00 0.02 0.00 0.03 0.14 0.00 0.03 0.13 0.00 0.07 0.00 0.00 0.06 0.23
N (R174)
C (A386)
0.07 0.60 0.00 0.00 0.00 0.03 0.00 0.07 0.00 0.00 0.00 0.15 0.00 0.00 0.00 0.02 0.02 0.00 0.04 0.00
0.13 0.00 0.00 0.00 0.00 0.07 0.05 0.00 0.00 0.08 0.00 0.00 0.00 0.00 0.53 0.06 0.00 0.00 0.00 0.08
N (H175)
C (G387)
0.05 0.59 0.03 0.00 0.00 0.00 0.00 0.02 0.10 0.00 0.00 0.05 0.04 0.04 0.00 0.02 0.04 0.00 0.03 0.00
0.10 0.00 0.00 0.00 0.00 0.00 0.02 0.73 0.00 0.00 0.00 0.00 0.00 0.00 0.06 0.03 0.07 0.00 0.00 0.00
N (G185)
C (L397)
0.00 0.00 0.00 0.00 0.00 0.00 0.00 1.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.09 0.07 0.00 0.00 0.00 0.00 0.17 0.00 0.05 0.29 0.00 0.02 0.09 0.00 0.13 0.08
N (F190)
C (V402)
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 1.00 0.00 0.00 0.00 0.00 0.00 0.00
0.11 0.00 0.00 0.00 0.03 0.00 0.00 0.07 0.00 0.02 0.00 0.00 0.13 0.00 0.00 0.06 0.30 0.00 0.00 0.28
N (gap)
C (gap)
0.03 0.07 0.09 0.00 0.06 0.04 0.00 0.24 0.05 0.03 0.02 0.00 0.00 0.09 0.00 0.02 0.00 0.00 0.05 0.21
0.00 0.00 0.00 0.68 0.00 0.00 0.26 0.00 0.06 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
(For the calculation of amino acid composition, Henikoff & Henikoff weight is used buy pseudocount is not introduced.）�
Clustering of the residues corresponding to
the selected alignment sites is statistically significant.
Aquaporin(1J4N) : Out of 249 residues, 50 residues constitute the pore surface. Out of the 16 residues corresponding
to the selected alignment sites, 11 residues are present on the pore surface.
M21, F24, I25, S28, I29, A32, L33, F35, H36, Q43, F58, I62, A75, H76, L77, N78, A80, V81, L85, S88, Q90,
T111, L114, T118, L121, N124, S125, G127, N129, T148, L151, V152, V155, L156,159, T160, R161,R162, I174,
V178, H182, G190, C191, G192, I193, N194, R197, S201, V226, R236
i
16−i
16! $ 50 ' $ 249 − 50 '
∑ i!(16 − i)!&% 249 )( &% 249 )( = 0.00003393
i=11
16
ClC chloride channel(1KPL) : Out of 451 residues, 36 residues constitute pore surface. Out of 14 residues corresponding
to the selected alignment sites, 5 residues are present on the pore surface.
€
V51, E54, S107, I109, P110, G146, R147, E148, G149, P150, T151, V152, A188, A189, F190, F229, N233, G234,
A236, I238, N270, V273, L274, Q277, D278, F317, F348, G355, I356, F357, A358, P359, M360, L444, Y445, I448
i
14−i
14! $ 36 ' $ 451− 36 '
∑ i!(14 − i)!&% 451)( &% 451 )( = 0.00351064
i= 5
14
extracellular region
€
cytoplasmic region
Different constraints are considered to have been working on
the interfaces against the extracellular and cytoplasmic environments.
Extracellular Region
Membrane
Pore Surface
Cytoplasmic Region
positive inside rule
Extracellular
environment
Cytosolic
environment
＋�
＋� ＋�
＋�
＋�
＋�
The efficiency to detect the residues related to positive-inside rule
was not so good.
The method was modified to increase the efficiency.
Reorganization of amino acid compostion
Ala Arg
Trp
0.01
0.05 0.03
Lys+Arg
remaining
0.012 0.988
site1 . . .
site i . . .
site L
Protein 1
Protein 2
Protein 3
��
Protein N
N-terminal
domain
Protein 1
Protein 2
Protein 3
��
Protein N
C-terminal
domain
Ala Arg
0.02 0.05
�
�
Trp
0.03
KLI between the two
domains is calculated
at each alignment site.
Lys+Arg
0.134
remainings
0.866
Distributions of KLI
160
100
140
90
80
120
70
100
60
50
系列1
80
系列1
60
40
30
40
20
20
10
0
-0.5 1 0.0 2 0.5 3 1.0
0
41.5
52.0
2.5
6
�aquaporin family
73.0
�
3.5
> 3.5
8
9
-0.5
1 0.0 2 0.5 3 1.0
41.5
52.0
62.5
73.0
83.5
>3.5
9
ClC chloride ion channel family
χ2 =28.110
χ2(2, 0.01) =9.21
χ2 =36.717
χ2(3, 0.01) =11.34
・The distributions do not follow the Γ distribution
・We used the kernel method to estimate the distribution non-parametrically.
Quaritc kernel is used for the estimation.
aquaporin
N
C
N
C
N
C
N
C
N
C
ClC chloride ion channel
(R12) c
(Q139) e
0.51
0.03
0.20 0.02 N (L77)
C (gap)
e
0.07
0.22
0.00
0.37
(F35) e
(R162) c
0.00
0.31
0.04 0.23 N (P80) e
C (G285) c
0.00
0.27
0.00
0.09
(V81) p
(R197) p
0.00
0.95
0.00 0.00 N (A90) ?
C (G295) ?
0.00
0.19
0.00
0.15
(L86) c
(S202) e
0.00
0.32
0.00 0.05 N (E113) c
C (P321) e
0.00
0.00
0.58 0.00 0.46
0.00
0.26 0.00 0.38
0.00
0.52 0.00 0.60
0.00
0.15 0.00 N (R175) c
C (G387) e
0.59
0.00
0.05 0.00 N (L212) c
C (P424) e
0.21
0.00
0.18 0.00 N (K216) c
C (T428) e
0.43
0.00
0.11 0.00 N (G234) e
C (gap)
0.00
0.07
R
0.00 0.33 K
(C89) c
(T205) e
0.25
0.00
N (R126) c
C (F335) e
0.04
0.00
N (R147) p
C (I356) p
N (R95) c
C (D210) e
0.41
0.00
R
0.18 0.00 K
N (R174) c
C (A386) e
N:N-terminal domain
C:C-terminal domain
c: cytosolic region
e: extracellular region
p: pore surface
extracellular
++++++
cytoplasmic
What we have learned from the study is …
Different glasses are required to see different constrains.
�
But, how to select a proper glasses ?
Ordinarily, we don’t have any prior knowledge about constraints.
�
Is it possible to make flexible glasses for any constraints?
Outline
1. 
2. 
3. 
イントロダクション
膜タンパク質のトポロジー反転
ケモカイン受容体
ケモカイン受容体
GPCRs
•  Membrane proteins
•  Bind neurotransmitters (physiologically
active peptides, amines, nucleic acids,
etc).
•  Ligand binding to GPCRs causes their
conformation changes.
•  It leads to several signal transductions
conjugated with trimeric G-proteins.
GPCRs
•  About 1000 genes in human genome
•  Target for ~45% of clinically marketed drugs
•  Divided into 5 classes based on sequence
similarity (Class A-E, the other)
•  Atomically resolved structure in class A GPCR:
Bovine Rhodopsin
デコイ受容体
リガンド結合能　○　○　△
シグナリング能　×　○
デコイ受容体
○
ケモカイン受容体ウイルス性受容体
機能的制約の違いを配列比較で検出できるのでは？
リガンド結合からシグナリングにいたるパスウェイの解明へ
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Evaluation of difference between two domains at each alignment site
Amino acid residue frequency
at the alignment site i in the
chmokine receptor
Site 1 . . .
Site i . . .
Ala Arg
0.05 0.03
Trp
0.01
Site L
Protein 1
Protein 2
Protein 3
��
Protein M
chemokine
receptor
�
Protein 1
Protein 2
Protein 3
��
Protein N
group of
decoy or viral
Kulback-Leibler information
between the two groups
calculated at each alignment
site.
receptor
�
Ala Arg
Amino acid residue frequency 0.02
at the alignment site i in the
a group of decoy or viral receptor
0.05
Trp
0.03
The difference between two probability distributions can be
quantitatively evaluated with Kulback-Leibler information (KLI).
(1) Definition of KLI
�
p(1)+p(2)+p(3)+ . . . +p(20)=1.0
20
Σ
p(i) log
i=1
p(i)
q(i)
(2) KLI representing the deviation of p from q is
different from that of q from p.
…
20
Σ
p(i) log
i=1
p(i)
q(i)
20
=
Σ
q(i) log
i=1
q(i)
p(i)
(3) Modified KLI is used in this study.
20
…
Σ
p(i) log
i=1
q(1)+q(2)+q(3)+ . . . +q(20)=1.0
p(i)
q(i)
+
20
Σ
q(i) log
i=1
q(i)
p(i)
デコイ受容体
ウイルス性受容体
Conclusion
重複遺伝子の機能差を調べることで
モチーフを調べること以上の機能的
情報を得ることがきでる。
分子進化に基づく生体機能の解析
Protein Informagics
Molecular Evolutionary
Genetics
Bioinformatics
Information Science
Developmental Biology
Genomics
Molecular Biology
Statistics
Structural Biology
Physics
共同研究者
1.
膜タンパク質のトポロジー反転
市原寿子　かずさDNA研究所
大安裕美　大阪大学
2. 
ケモカイン受容体
大安裕美　大阪大学
根本　航　東京電機大学

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