Istvan SIMON Institute of Enzymology, BRC Hungarian Academy of

1
e,——
and cultural
the
abdus salam
international centre for theoretical physics
international a
energy agency
SMR 1329- 1
COLLEGE ON BIOPHYSICS:
FROM MOLECULAR GENETICS TO STRUCTURAL BIOLOGY
1 - 12 OCTOBER 2001
PREDICTION OF TRANSMEMBRANE
PREOTEIN TOPOLOGY
Istvan SIMON
Institute of Enzymology, BRC
Hungarian Academy of Sciences
XL Karolina uut. 29
H-1518 Bp, Budapest, Hungary
These are preliminary lecture notes, intended only for distribution to participants.
strada costiera, I 1 - 34014 trieste italy - tel.+39 04022401 I I fax +39 040224163 - [email protected] - www.ictp.trieste.it
Cytochrome BCl Complex (Ibgy)
-20
Inside
Polarity scale for identifying
tnmsmcmbrane helices
Amino mid
residua
Transim frm &nergy
(kcal/mol)
Ph#
Met
lie
Leu
Vat
Cys
Trp
Ala
Thr
Gly
Ser
Pro
Tyr
His
Gin
Asn
Glu
Lys
Asp
Arg
3.7
3.4
3,1
2.8
2.6
2.0
1.9
1.6
1.2
1.0
0,6
-0.2
-0,7
-3.0
A 1
**. 1
-4.8
-8.2
-8.8
No(e: Ttte free energies are for the
transfer of an amino acid residue in an a
helix tV»m the membmnc inferior
(ussiimccl Ut have ;i dielcttiic ctHisiani <>{'
2} lo iviitcr. After D.M. Kngchnati, T.A.
Steitz, and A. Goldman. Ann, Rrv,
Bhphys. Bwpftys, Che»L 1
Single a-helix
in glycopterin
0
20
40
60
80
100
First amino acid residue in window
Hydrophobieity
Hydrophobicity
Hydrophobicity
Hydrophobicity
Hydrophobicity
Hydrophobicity
Hydrophobicity
Hydrophobieity
t
£^
C^
.1 . .... ...i
f^
t,
t
f
I
to
p
o
; . . / . ' • • ! • : • •
s
OS
120
ISO
240
COX3_PAR0B.sw
1, DAS plot of two arbitrarily chosen proteins (COX3_PAR©il
CYDMmPXX)tl). The cmss weighted cumulative score profile (<km$&
l lg}ot>s! DAS profile (continuous line) calculated as tie SWmga W
scow profiles attained for compsrisofts with the 6#&'r 43
iii &n& test set are also shown for>COX3_PA^t>1i.
W
CYt>B_E€OL! has eight tnmsmembratte s
F =
5
E
20
E
J. J
log
X
where pj is the frequency of the residue j
in the whole protein;
lj is the frequency of the residue j in the
structural part i of the protein.
QmtM&eloop
Outside
Inside
Xn»ide loop
Amino acid seq: MGDVCDTEFGILVA. - .SVALRPKKHGRWIV. . .PWVDNGTEQ. • .PEHMTKU-IMM. . .
State seq:
ooooooooohtihhh.--hhhhiiiiiiihhh...hhhoooooo...ooooooohhh..Tail
Tail-Tuil,
Tail- Loop -Tail
f—
Topology:
out
Short lo&p
Long loop
lugure 2. Stmctural states tklined for a typical helical trammembrane protein, rl1\e five states are: inside loop (I),
inside tail (i), membrane helix (h), outside tail (a) and outside loop (O). Tails (tliick lines) are thought tQ interact with
the inside or outside parts of the membrane, while loops {thin lines) do not Two tails between helices can form a
short loop, but longer loops are formed by tail-loop-tail sequences.
MM
00
Figure 3. Architecture of UMM
used for topology prediction. States
with the same transition matrices
are colored in the same way: whit*?,
helix states; light gray, tail states;
dai'k gray, loop states. Rectangular
areas 'FL type states; tiexagona!
ones, NFL type states. The observation-symbol probaMities used by
states are -marked in each state. The
structure of stfbsta1?es m. #ie case of
the iPL *bj^pe is drawn wWfcin states.
Lines and arrows show $*e possible
'transition between states or substates.
/ Chetn. Inf. CompuL $ci.t Vol. 41, No. 2, 200}
TOPOLOGY or MEMBRANE PROTBINS
•18
0
18
0
100-
• 100-
17
"X
DSSP
-13
100
0
13
'12
TMAP
;sidei
Inside
-60 -40 -20 0 20^ 40
z-coordinates (A)
1
100
Outside!
0 (Inside
-60 -40 -20 0 20 40 60
z-coordinates [A]
60
16
O
100- SOS 11
"S50 -
-40 -20 0 20, 40
^-coordinates [A)
I
60
15
— - - --|
60
A
sSPLIT
100-
j
0
-—
60
H
TMjprcd
i
-60 -40 -20 0
20, 40
a-coordinat-es IA|
IMKMSAT
\
-14
iiO
0
•4Q -40 -20 0 20, 40
2-coordinates {A]
60
100 ~rTOPPRKU...
J
g
.
-350-
"Z60-
.Outside
instde
'
60
1
60
Inside ^J :
0-60 -40 -§0 0 20 T 40
z- coordinates [A]
0-
100 -T-
100-;-
..„>
t
-14
«
-14
HAS
-60 -40 -20 0
20, 40
7,-coordinates |A)
TMHMM;
-60 -40 -20 0 20 r 40
^-coordinates tA)
-60 -40 -20 0
20 s <«)
z-coordinates f A]
Outside
0 4J
PHDhtm
Vouuido
I0U-
A.
"7TT
^
-15
12
15
N
/
J5O-
o-
2
367
\
!
•
1
•
s
"
T
•
7
-60 -40 -20 0
20, 40
z-coortiinates [A)
OuUrde
I
60
-60 -40 -20 0
20 40
^-coordinates (A|
60
-#9 -20 O 20 40
x-coordinates fAi
60
Figure 2. Disuibution of transmembrane helices measured parallel to the average direction of the n&MSiefflterai« helices in 1 A slices in
the eight selected proteins (see the text). Tramrnembrane helices are defined by the DSSP program and predicted by various transmembrane
helix prediction methods. The ^-coordinates at the value of 50% and at the mean of the curves are shown atoow the graphs. The gray areas
show the same regions as in Figure I.
dOJJWVH
c
sva i 11
JOXKKH
3
r-i
o
sva
r
aanddox
-
O
*O
O
CJ
a
r--
sv
O
o
! ©
in
r-i
e
© I
<y
sva
o
r-;
'S
a
Q
*
x
O
o
»; P
o
sva
j->,
^
I
£
s
t
10
a i
JJN
i^j.
SO
L
i_fc
C^
C^
C1^-
Globular proteins
FUtuUtedio
-CI*A_BACTK
c
jt'
*"••>.;;,
5 . ••„.-• s- ••
C9CA.BACTO
;>*Sf,
F1SP.ANASP
. VAflB.ACICA
30 40 SO 60 IB SO M 100
S i d i
I 100 20O 300 4 » 300
663
IB 40 50 60 TO 80 90 100
I
•
If
•
eeqpence number
1
too
mo
3Ji
Prion proteins
i
PR HI Hl'MAN
?RIO_TT111T
FIUO.CHICK
•c
JO «
SO MJ ?tt SS 90 HIE)
14 identity
1
1
I
!
I
1
tOO
3(*J
2»
Transmembrane proteins
Gip tunctiiw fW protein
f tonsport ptotein
rtnploi
• ' * : •
TO1XJ_ECW-I
•
•c
KXEB.ECOl.I
1
too
200
300
607((g
tiidontity
•Si
:ia
EVBBJALTi'
EXBB^SEFU
30 40 M 60 711 10 90 M»
*
0
TOLy^CSLAE
MSm
I(K1
2O024S
30
4O$0U70«D90
I
]«0 200 3M 4«l
Sil
Outside
Inside
C
rapid evotatlsB
B
N *- - .
SI
'»J*,
«-*..
A
12
„.'
Slow evol
Outside
Conimon energy landscape
\ , \ of a globular or a transmembrane protein*
| One stable state
Cellular rel&ealizatiom
Energy landscape
corresponding to
the transient state
from traiisinejiiijrane
protein to globular one.
Two (or more) stable state
13