T I B S - A u g u s t 1 982

288
immunoprecipitate the antigen from cell
lysates. Therefore, T lymphocytes that
undergo increased DNA synthesis and cell
proliferation express HLA-DR. This has
important implications in the co-operative
interactions among B and T lymphocytes in
regulating the immune response.

Conclusions
In summary, the polymorphic HLA-DR
antigens are a group of cell surface glycoproteins with limited tissue distribution.
They are found predominantly on B lymphocytes; notable exceptions include some
tumor cells (e.g., melanoma) and activated
T lymphocytes. These antigens consist of
two chains, with apparent mol. wt of
34,000 and 28,000. The 28,000 mol. wt
chain contains the observed heterogeneity
of the intact molecule. During their biosynthesis it appears that the HLA-DR antigens
undergo conformational changes, aided in
part by their oligosaccharide moieties. The
surface density of these antigens is maximal

during the G2 phase of the cell cycle. We

are just beginning to understand these
molecules, aided greatly by the power of
MoAbs. which serve as well defined probes
to dissect and characterize these antigens.
References
I Eerrone, S., Allison, J. P., and Pellegfino, M. A.
(1978) Contemp. Top. Mol. lmmunol. 7,
23%281
2 Terasaki, P., ed. (I 980) Histocompatibility Testing, Munksgaard, Copenhagen
3 Allison, J. P., Walker, L. E., Russell, W. A.,
Pellegrino, M. A., Fen'one, S., Reisfeld, R. A.,
Frelinger, J. A. and Silver, J. (1978) Proc. Natl
Acad. Sci. U.S.A. 75, 3953-3956
4 Corte, G.. Damiani, G., Calabi, F., Fabbi, M. and
Bargellesi, A. (1981) Proc. Natl Acad. Sei.
U,S.A. 78, 534-538
5 Shackelford, D. A. and Strominger, J. L. (1980)
J. Exp. Med. 151, 144-I65
6 Silver, J. and Fen'one, S. (1979) Nature (London) 436-437
7 Accolla, R. S., Gross, N., Carrel, S. and Cone, G.
(1981) Proc. Natl Acad. Sei. U.S.A. 78.
4549-4551

The architecture of photosynthetic

membranes: lateral and transverse
organization
Jan M. Anderson and Bertil Andersson
There is a m a r k e d transverse a s y m m e t r y in the organization o f the supramolecular
complexes involved in light-harvesting, electron transfer a n d p r o t o n translocation in
chloroplast thylakoid membranes. Additionally, in chloroplasts containing grana
stacks (appressed thylakoids), there is an extreme lateral a s y m m e t r y in the
distribution o f m o s t complexes between the stacked and unstacked m e m b r a n e
regions.

The concept of two photosystems cooperating in series to transport electrons

from I--I~Oto NADP-, depicted by the familiar Z scheme, has been the comer-stone of
modem photosynthesis. The components
of the two photosystems involved in lightharvesting, electron flow and proton translocation are highly organized in the fluid
bilayer of the thylakoid membranes of
chloroplasts. This review concentrates on
the distribution of these components across
and along the membrane with special
emphasis on results from inside-out
thylakoid vesicles. We will also focus on
the consequences of recent experimental
findings, which demonstrate a lateral separation of photosystems, for the photosynthetic process and its regulation.

Components of thylakoid membranes

Many of the 30-50 thylakoid polypeptides are arranged in at least five supramolecular membrane-spanning complexes,
three of which are directly involved in electron transport (Fig. 1)L The photosystem II

8 Kohler,G. and Milstein, C. (1975)Nature (London) 256, 495-497

9 Owen, M. J., Kissonerghis,A.-M., Lodish,H. F.
and Crumpton,M. J. (1981)J. BioL (?hem. 256,
8987-8993
10 Walsh, I:LS. and Crumpton,M. J. (1977)Nature
(London) 269, 307-311
I I Glassy,M. C. and Ferrone,S. (submittedfor publication)
12 Wilson,B. S., Glassy, M. C., Quaranta, V., Ng,
A.-K. and Ferrone,S. ( 1981)Scand. J. ImmunoL
14. 201-205
13 Owen, M. J., Kissonerghis,A.-M. and Lodish,
H. F. (1980)J. Biol. Chem. 255, 9678-9684
14 Shackelford, D. A.. Lampson, L. A. and
Strominger, J. L. (1981) J. lmmunol. 127,
1403-1410
15 Sarkar, S., Glassy, M. C., Ferrone. S. and Jones,
O. W. (1980) Prec. Natl Acad. Sci. U.S.A. 77,
7297-7301
16 Lee. J. S., Trowsdale, J. and Bodmer, W. F.
(1982) Prec. Natl Acad. Sci. U.S.A. 79,545-549
17 Lloyd, K. Oi, Ng. J. and Dippold, W. G. (1081)
J. Immunol. 126, 2408-2413
IS Evans, R. L.. Faldetta, T. J., Humphreys,R. E.,
Pratt, D. M., Yunis. E. J. and Scltlossman,S. E.
(1978)J. Exp. Med. 148, 1440-1445
complex includes at least two intrinsic
polypeptides (40,000-50,000 mol. wt)
which bind the reaction centre chlorophyll
P680, antennae chlorophyll a and
/3-caroteneL This complex probably also
contains electron donors and accepters,
cytochrome b-559.P and a herbicidebinding polypeptide of mol. wt 32,000.
The photosystem I complex contains a
polypeptide of mol. wt 68,000 and several
smaller polypeptides:L It also contains the
reaction centre chlorophyll I>700, electron
accepters, antennae chlorophyll a and
fl-carotene. Between these two complexes
is the recently isolated cytochrome b / f
complex which is analogous to the cytochrome b/c complex of photosynthetic bacteria and mitochondria 4. The thylakoid
complex is comprised of one cytochromef,
two cytochrome b-563, one Fe-S centre and
a polypeptide of mol, wt 17,00(P. These
three complexes are linked by mobile electron carriers, plastoquinone, plastocyanin,
H

stroma
ADP+Pi

_thylakoid ~ ' ~
rnernb ....

~=~'-~'PQ\I~'

F~ PS2 ~

)1FeS I

I1

, ,~f~S

A ,~
TP

NADP~- / --~ ~

PSl ~1J

~I}

CFo

2t02 2H+~. . . . .
2H+-- . . . .
->H+
Jan M. Anderson is at the Division of Plant Industry, CSIR O, P.O. Box 1600, Canberra City, A. C. T.
inside
2601, Australia and Bertil Andersson is at the
Fig. 1. Schematic representation of photosynthetic electron flow ( - - ) and proton transport (. . . . . . . . ) in
Department of Biochemistry, University of Lund,
thylakoid membranes.
S-220 07 Lund, Sweden.
ElsevierBioraedicalPres~1982 O376 5067182/0(XX)(k'~Xll$(lt(WI

289

T1BS - A u g u s t 1982

and ferredoxin. Electron transport through

both photosystems results in the reduction
of NADP + and the transport of protons
from the outside to the intrathylakoid space.
This proton gradient is used by a fourth
complex for making ATP. ATP synthetase
consists of hydrophobic membrane sector
(CFo) and a peripheral coupling factor
(CF1)S. The fifth complex has no catalytic
activity itself; its primary function is to capture solar energy. This light-harvesting
complex (LHC) contains at least two main
polypeptides of mol. wt about 25,000
which bind up to half of the total
chlorophyll a and nearly all of the
chlorophyll b molecules6. Most of this
complex is associated with photosystem II
(LHC2) but recent evidence suggests that
photosystem I also has specific chlorophyll
a/b-proteins (LHC~). Further evidence also
suggests that LHC= is involved in the
molecular mechanism of thylakoid stackingL
The supramolecular complexes are
embedded in the bilayer to form a fluid
lipid-protein mosaic membrane. Lipids
make up 50% of the thylakoid mass. Interestingly, traditional phospholipids comGrana t hyiakoid
end membrane
((

.....

111111111111

)) . . . .

..........

>)

gm

partition

St . . . .

thylakoid

......................
Thytakoid breakage by
Yeda press disrupbon

;--:-/:::----:-3,

,,

Membrane resealing
and vesicle formation

Phase partition

@o@
~

upper
phase

lower
phase

/
$1roma
exposed

out
i-,, -I appressed
in

Fig. 2. Isolation of inside-out vesicles originating

from appressed thylakoids following Yeda press
fragmentation and aqueous polymer two-phase
partition.

prise only a very small fraction of the total turned inside-out- revealed functionally by
lipid; 80% is neutral galactolipids. Most of their reversed proton and elecL~cal gradthe acyl chains of these lipids have an ients and structurally by freeze-fracture
unusually high degree of unsaturation mak- analysiss. Furthermore, the inside-out vesicles are derived from the grana appressions
ing the thylakoid bilayer very fluid.
A striking structural feature of the as judged by their freeze-fracture particle
thylakoid membranes of most plants and pattern and mode of formations. Fig. 2
some green algae is their differentiation into illustrates how Yeda press treatment rupstacked (appressed) and unstacked (non- tures the grana stacks at their margins, with
appressed) regions (Fig. 2). The outer the attractive stacking forces keeping adjamembrane surfaces of these two regions are cent membranes of the granum appressed.
different, since only the stroma thylakoids Inside-out vesicles form when such appresand the end membranes and margins of sed membrane pairs reseal, while nongrana stacks are in direct contact with the appressed membranes seal right-side out.
chloroplast stroma, the closely appressed
membranes of the grana partitions having Transverse organization of some
limited contact with the stroma. In contrast, thylakoid components
There is some evidence for a vectorial
thylakoids enclose an inner space which is
continuous between appressed and arrangement of the electron transport carstroma-exposed regions. As will be discus- riers, suggesting that the electron donor
sed later, this structural differentiation is sites for both photosystems 1 and II are
accompanied by a functional differentia- located towards the inner thylakoid surface
and the electron acceptor sites at the outer
tion.
surfacex. Such an orientation is required to
explain vectorial electron transport by each
Subfractionation of the thylakoid
photosystem and the inward direction of
membrane
Much of the information concerning the proton pumping. The recent isolation of
organization of thylakoid membranes has inside-out vesicles has been useful in
been obtained from fractionation studies. clarifying certain points concerning the
Thylakoids have been fragmented by transverse asymmetry of thylakoids. The
detergents or mechanical sheafing and vari- inner surface of inside-out vesicles can be
ous centrifugal techniques have been used directly probed by suitable membraneto separate the thylakoid fragments7. Typi- impermeable effectors and compared with
cally, the light fractions contain vesicles the outer surface.
The location of the water-splitting site
derived mainly from stroma thylakoids and
have only the properties associated with has been one area of controversy. Trypsin
photosystem I. The heavy fractions are proteolysis of control thylakoids effectively
derived from more or less intact grana inhibits photosystem II activity. This is also
stacks and contain both photosystems. the case for trypsin digestion of inside-out
These traditional separation approaches thylakoidss. However, addition of an artififailed to give membrane fractions represen- cial electron donor, diphenylcarbazide
tative of the grana appressions without any (known to bypass water-splitting) restores
non-appressed grana end membranes and the activity completely in inside-out, but
margins. Moreover, traditional subfraction- not in fight-side-out vesicles. This clearly
ation methods failed to provide thylakoid shows that the water-splitting site is located
membranes which were turned inside-out. at the inner thylakoid surface. Another way
Such inside-out vesicles have been of great to destroy photosynthetic water-splitting
importance for biochemical investigations consists of Tris-washing, which releases
of the transverse asymmetry of other polypeptides of mol. wt 33,000 and 23,000
from the inner thylakoid surfaces. This
biological membranes.
Both these fractionation problems were suggests the possible identification of the
solved by the introduction of aqueous rust components of the water-splitting reacpolymer two-phase partition for subfrac- tion whose composition has so far remained
tionation of the thylakoid membranes. The unknown.
Another area of dispute concerned the
phase partition technique allows membranes to be separated into the upper or location of plastocyanin, since the original
lower phase according to differences in sur- suggestion that plastocyanin was located at
face properties9. Two membrane popula- the inner thylakoid surface was later contions are resolved from thylakoids frag- tradicted. Therefore, the effect of purified
mented in a Yeda press, one with a high plastocyanin on photosystem 1 electron
affinity for the upper phase and the other for transport was compared with vesicles of
the lower phase. The thylakoids which par- opposite sidednessH. P700 was rapidly
tition to the upper phase show normal reduced by externally added plastocyanin
right-side-out properties. In contrast, the with inside-out vesicles only. Moreover,
lower phase contains vesicles which are immunological analysis showed that plas-

TIBS -August 1982

,nin was readily released from inside)ut not from right-side out vesicles.
e observations verify that plastocyanin
eripheral protein loosely bound to the
thylakoid surface.
any membrane proteins actually
rse the membrane. While the existence
tch membrane-spanning proteins and
flexes in thylakoid membranes had
suggested, the lack of inside-out vcsimade experimental verification dif:. Recently, in collaboration with Dr
Ryrie, we demonstrated that the
-harvesting chlorophyll-protein comis indeed a membrane-spanning com2. An antibody against either purified
elipidated light-harvesting complex
:ed heavy agglutination when mixed
her with either right-side-out or
e-out
vesicles
prepared
from
koids of uniform composition. The
~rum was also pre-incubated with
cked thylakoids to remove antibodies
~st the outer membrane surface regthen the supernatant was tested for
ntination with both vesicle types. With
~retreated antiserum, agglutination of
.side-out vesicles was greatly reduced,

but the inside-out vesicles were agglutinated. This clearly shows that the lightharvesting complex traverses the membrane exposing different antigenic sites at
the outer and inner thylakoid surfaces.

Lateral asymmetry of thylakoid

membranes
The location of ATP synthetase in
grana-containing chloroplasts was established in 1976 by Miller and Staebelin ~3,
They used electron microscopy to demonstrate that the chloroplast coupling factor
was present only on the outer surface of
stroma-exposed thylakoids. The early fractionations of thylakoids clearly showed that
photosystem I was enriched in stroma
thylakoids while the grana stacks were only
slightly enriched with photosystem 117.
Analyses of the inside-out vesicles showed
that the grana partitions are much more
enriched in photosystem II than in intact
grana stacks 14. However, at the time it was
not possible to demonstrate how much of
the chlorophyll was associated with either
photosystems I or II. This can now be done
by mild SDS-PAGE methods, since nearly
all the chlorophyll remains bound to protein6.

We therefore isolated thylakoid subfractions representing grana stacks, grana partitions (inside-out vesicles) and stroma
thylakoids and compared their relative content of the three main chlorophyll-protein
complexes ~5. These results are summarized
in Table I which also includes analyses of
the cytochrome b/f complex TM and ATP
synthetase17. Most of the photosystem 11
complex and light-harvesting complex is
located in the appressed membranes, with
only 10-20% in the stroma-exposed membranes (Fig. 3). In contrast, most of the
photosystem I complex is located in the
stroma-exposed thylakoids. The low contribution of P S I complex seen in the
inside-out vesicles may be due to contain[nation with stroma-exposed thylakoids (as
judged by CF1 determinations 17 and the
proportion of P700 slowly reduced by plastocyaninas). Hence, it may be that the grana
partitions contain no photosystem I complex. This is also indicated by a recent
improvement of the phase partition procedure which yields grana partition vesicles
that have hardly any photosystem I complex TM. Such an extreme distribution is suggested also by a freeze-fracture study with a

,L,
S

Piq~ro N POOL
.,.,,

~s

by -I~8.

,.--

TIBS - August 1 982

/./

TABLE1. Relativecontentof the five intrinsiccomplexesin thylakoidsubfractionsrepresentingdifferentrnem- trons are transferred from photosystem
photosystem I. At first sight the most
braheregions
vious candidate for a lateral shuttle is lc
Thylakoid
PhotosysternI Photosystem11 Light-harvesting Cytochromeb/f
ATP
toquinone, since re-oxidation of pl~
fraction
complexa
complex"
complexa
complexb
synthetase: quinone is the rate-limiting step in ph
synthesis, With a half-time of 20 ms (I
Unfractionatedthylakoids
30
13
52
460
4.2
10). While the large pool of plastoqui~
Granastacks
20
13
60
3.4
molecules would be mobile in the m
Granapartitions
(inside-outvesicles)
10
14
65
470
1.2
brane, the uniform distribution of
Sla'omathylakoids
69
5
17
485
I 1.7
cytochrome b / f complex means that sq
electrons would have to be transferred f
a% of total chlorophyll(Ref. 15);bChl/cytfratio(Ref. 16); cArbitraryunits(Ref. 17)
the cytochrome complexes of appre:
photosystem I mutant of maize =. A ATP synthetase and the contrasting membranes to nearby photosystem I c
mechanism for the exclusion of photosys- uniform distribution of the cytochrome b / f plexes in stroma-exposed membra
complex between appressed and stroma- Hence plastocyanin may also be a liP,]
tem I complex from the grana partitions
based upon electrostatic repulsive forces exposed thylakoids has profound conse- lateral shuttle. Plastocyanin, which h
role analogous to that of cytochrome
has been postulated by Barber2L In marked quences for photosynthesis (Fig. 3).
inner mitochondrial membranes, cq
contrast to the asymmetric location of the
either diffuse laterally while still attach~
chlorophyll-protein complexes and ATP Electron transport
Since two of the three membrane com- the membrane or diffuse very rapidly it
synthetase, the cytochrome b / f complex is
uniformly distributed between the different plexes involved in electron transport are not intrathylakoid space which is contint
thylakoid regions (Refs 16, 22, Paterson, uniformly distributed between stacked and between grana partitions and strc
D. and Wraight, C. A. private communica- unstacked regions it is clear that single exposed thylakoids.
structural electron transport chains cannot
The third, but less likely, possibility :
tion).
exist. This was evident, from the lack of lateral shuttle between appressed and
constant stoichiometry between the various appressed regions is the cytochrome
Consequences of lateral asymmetry
The extreme lateral asymmetry of the thylakoid components, seen for example in complex itself. However, Hackenbre
chlorophyll-containing
complexes and the varying chlorophyll/P700 molar ratios has calculated for inner mitochon~
of different plant chloroplasts 1. Moveover, membranes that the relative distances
Melis and Brown2a have shown that the fused by large membrane complexes a
ratios of PS II reaction centres to PS I reac- least two to three orders of magnitude sl
tion centres are rarely unity. Now that the ler than those of the linking compon~
concentrations of various components cytochrome c ubiquinone. Similar cal
involved in electron transport are being tions also suggest that both plastoquil
measured in many different chloroplasts it and plastocyanin could move with d:
is obvious that there is not necessarily a sional velocities great enough to allow
fixed and constant stoichiometry between tron transport.
them. Further, the existence of intrinsic
complexes as structurally independent Light-harvesting
entities in the native membrane is demonContrary to popular notions that
strated since these can now be isolated as chlorophylls of photosystem II and ph,
supramolecular complexes. Thus, while system I are in contact with each other,
the composition of each individual complex data show that most of the chlorop
remains fixed, the relative proportions of domains of photosystem 1I are widely :
each may vary with respect to one another. arated from those of photosystem Ia~,2
Since there are no fixed electron trans- chloroplasts that have grana stacks. "
port chains we need to consider how elec- means that the transfer of extra light en~

PS1 complex - LHC 1

ATPsynthetase

PS 2 complex - LHC 2

Cytochrome b_f complex

Fig. 3. Distributionof thylakoid complexesbem,eenappressedand stroma-exposedthylakoids.

T I B S - A u g u s t 1982

292
from photosystem II to photosystem I, the
so-called 'spillover', is largely prevented ~.
How, then, do grana-containing chloroplasts regulate the distribution of light energy
between the photosystems? Allen et al. 26
suggest that the reversible photophosphorylation of the outer surface-exposed threonyl
residues of the main polypeptides of the
light-harvesting complex may he implicated. Recently, Barber'7 suggested that the
phosphorylation of some of the photosystem II - light-harvesting complexes would
increase their net negative charge thereby
causing them to move from the appressed
membrane regions to stroma-exposed
thylakoids. This would result in a decreased
extent of appressed membranes and allow
more of the light-harvesting complex to
interact with photosystem I complex,
thereby facilitating light-sharing. Hence,
spatial separation of the photosystems in
combination with phosphorylation would
he one way for the controlled regulation of
light energy distribution between the two
photosystems.
Function o f different chloroplasts
Structurally independent thylakoid complexes linked by mobile electron carriers,
plastoquinone, plastocyanin and ferredoxin, allow great flexibility in the actual
photosynthetic rates achieved by various
membranes. This can be illustrated by a
brief comparison of sun and shade plants 1.
Sun plants have high rates of photosynthesis per unit chlorophyll and much higher
ratios of stroma-exposed to appressed
membranes than shade plants. Because of
the marked lateral heterogeneity of the
complexes, this means sun plants have
higher amounts of photosystem I complex
and ATP synthetase, hence greater rates of
photosynthesis. On the other hand, shade
plants, which receive only limited illumination, need to have greater amounts of
photosystem II and light-harvesting complexes. Shade plants have giant grana
stacks and only limited areas of stroma
thylakoids, hence they have less photosystern I complex and ATP synthetase; in turn
they have much lower rates of maximal
photosynthesis, which are saturated at
lower light intensities than in sun plants ~.
Lateral asymmetry in the distribution of
complexes ensures great versatility in the
functioning of photosynthetic membranes,
an important factor for plants which must
exist in a great variety of environmental
conditions.

References

3 Mullet, J. E., Burke, J. J. and Arntzen, C. J.

(1980) Plant Physiol. 65, 81-84
4 Hurt, E. and Hanska, G. ( 1981) Eur. J. Biochem.
117, 591-599
5 Nelson,N. (1981)Curt. TOp. Bioenerg. I1.1-33
6 Anderson, J. M., Barrett, J. and Thorne S. W.
11981) in Photosynthesis (Akoyunoglou. G..
ed.), Vol. lit, pp. 301-315, BalabanInternational
Science Services,Philadelphia
7 Hiller, R. G. and Goodchild, D. J. (1981) in The
Biochemistry of Plants (Hatch, M. D. and
Boardman, N. K., eds), Vol. 8, pp. 1-49,
AcademicPress, New York
8 Andersson, B., Akerlund, H.-E. and Albertsson,
P.-A. (1981) in Photosynthesis (Akoyunoglou,
G., ed.), Vol. HI, pp. 55-66, Balaban International ScienceServices, Philadelphia
9 Albertsson, P.-A. 11978) Trends Biochem. St'i.
3, N 37-39
10 win, H. T. (1975) in Bioenergetics of Photosynthesis (Govindjee, ed.), pp. 493-564, Academic
Press, New York
I l Haehnel, W., Berzborn, R. J. and Andersson. B.
(198l)Biochim. Biophys. Acta 637,389-399
12 Andersson, B., Anderson, J. M. and Ryrie, 1. J.
11982) Eur. J. Biochem. 123.465-472
13 Miller, K. R. and Staehelin, A. 11976) J. (~ll

Biol. 68, 30.-47

14 Akedund, H.-E., Andersson, B. and Albertsson,
P.-A. (1976) Biochim. Biophys. Acta 449,
525-535
15 Andersson, B. and Anderson, J. M. (1981))
Biochim. Biophys. Acta 593,427-440
16 Anderson,J. M. (1982)FEBS Lett. 138, 62-06
17 Berzborn, R. J. Muller. P.. Roos, P. and
Andersson, B. in Photosynthesis (Akoyunoglou.
G.. ed.), Vol. Ill. pp. 107-120, Balaban International ScienceServices, Philadelphia
18 Andersson,B. and Haehnel, W. (in preparation)
19 Henry, L. E. A. and Lindberg-Moller,B. 11981)
Carlsberg Res. Commun. 46, 227-242
20 Miller, K. R. (1980) Biochirn. Biophys. Acta
592, 143-152
21 Barber, J. (1980)FEBS Lett. 118, 1-10
22 Cox, R. P. and Andersson, B. 11981)Biochem.
Biophys. Res. Comrnun. 103, 1336-1341
23 Melis, A. and Brown, J. S. (1980) Proc. Nad
Acad. Sci. U.S.A. 77, 4712-4716
24 Hackenbrock, C. R. (198I) Trends Biochem.
Sci. 7, 151-154
25 Anderson,J. M. (1981)FEBS Lett. 124, 1-10
26 Allen, J. F., Bennett, J., Steinback, K. and
Amtzen, C. J. (1981) Nature (London) 291.
21-25
27 Barber, J. (1982) Bioscience Reports 2, 1-13

Structure of intrinsic membrane

proteins
Roderick A. Capaldi
Several intrinsic m e m b r a n e proteins have non, been characterized in s o m e detail.
These are all p o s i t i o n e d in their respective m e m b r a n e s by one or m o r e
t r a n s m e m b r a n e , h y d r o p h o b i c , helical a m i n o acid stretches.

Biological membranes are composed of

lipids, proteins and carbohydrates. The
lipids are arranged as a bilayer with their
polar head groups on the outside and their
fatty acid tails on the inside, providing an
essentially hydrocarbon interioP .2. Proteins
which are integrated into this continuum are
called intrinsic membrane proteins to distinguish them from those associated with
the surface of the bilayer (extrinsic membrane proteins)l.L The carbohydrate in
membranes is bound covalently to either
protein or lipid molecules in conjugates
called glycoproteins and glycolipids.
Intrinsic membrane proteins are involved
in many regulatory and metabolic processes
including cell-cell interaction and recognition, hormone stimulation, vectorial transport of ions and metabolites, oxidative and
photo-phosphorylation and lipid biosynthesis. Our understanding of these cellular
functions would be greatly enhanced if the

I Anderson,J. M. (1982)Mol. C~ll Biochem. (in

press)
2 Satoh, K. 11981) in Photosynthesis (Akoyunog- Roderick A. ( apaldi is at the Institute of Molecular
lou, G., ed.), Vot. IIi, pp. 607-616, Balaban Biology, University of Oregon, Eugene, OR
97403, U.S.A.
InternationalScience Services, Philadelphia
ElsevierBiomedicalPress1982 O376- 5067/82/00(X1 (XX)0/$01(x)

structure of the proteins involved were

known.
So far no intrinsic membrane protein has
been crystallized in a form suitable for high
resolution X-ray crystallography, instead,
our present picture of these proteins is based
on inferences drawn from the structures of
water-soluble proteins and from the low
resolution structural data collected from a
few easily purified examples.

General features of proteins and

constraints on the structure of
membrane proteins
It is well established that the threedimensional structure of a protein is a consequence of its amino acid sequence.
Polypeptides fold into secondary structures, helices a n d / 3 structures which are
separated by lengths of non-regularly
arranged backbone. These secondary structures pack together, often into globular particles, directed by thermodynamic forces
including hydrophobic interactions, hydrogen bonding requirements and the hydration needs of charged groups :~.