Integral & Peripheral membrane proteins Helical membrane proteins could be single pass /multi pass porins which are beta sheets ion channels.

1. Membrane Proteins

2. Membrane Proteins
Lipids form a permeability barrier and establish compartments but membrane
proteins are essential for most membrane functions…..
 myelin: a lipid-rich membrane (25% protein) - insulates nerve fibers
 plasma membranes: location of pumps, channels, receptors – 50% protein
 energy transduction membranes: mitochondria, chloroplasts - 75% protein
 about 30% of the proteins in an animal cell are membrane proteins
•Proteins can be associated with membranes in several different ways
•Membrane proteins have asymmetric orientations in membranes
•Proteins have very slow rates of movement –slower than lipids
•Membrane protein’s soluble form is critical to function (e.g. lipid kinases, lipid
phosphatases, coat proteins)…. Lipids help them to stay soluble

3. Functions of membrane proteins
• Transport of nutrients
• Passage of water
• Selective transport of molecules
• Maintenance of proper ionic composition inside the cell
• Reception of signals from the extracellular environment
• Expression of cell identity
• Physical and functional connection with other cells or extracellular
matrix (in multicellular organisms)

4. Various ways proteins associate with lipid
bilayer
• Transmembrane proteins (Integral) : cross bilayer in various ways;
1. As a single α helix
2. as multiple α helices, or
3. as a rolled-up β sheet (β-barrel)
4. Membrane proteins exposed to cytosolic side but anchored into cytosolic
monolayer an amphiphilic α helix
• Transmembrane Lipid Anchored Proteins:
1. Some “single-pass” and “multipass” proteins covalently attached via fatty acid
chain inserted in cytosolic lipid monolayer
• Lipid Anchored Proteins: attached solely by a covalently bound lipid chain;
5. a fatty acid chain or a prenyl group in cytosolic monolayer or
6. an oligosaccharide linker to phosphatidylinositol in noncytosolic monolayer
• Membrane-associated proteins (Peripheral): attached on outer surface of
membrane by non-covalent interactions with
7. transmembrane membrane proteins on cytosolic side or
8. transmembrane membrane proteins on extra-cytosolic side
Figure 10-19 Molecular Biology of the Cell (© Garland Science 2008)

5. Figure 10-19 Molecular Biology of the Cell (© Garland Science 2008)
3-D View of Membrane Embedded Proteins

6. Structural conformation of
transmembrane proteins?
Two ways for a protein to cross a biological membrane:
1.α helix – satisfies hydrogen bonding requirements of peptide
backbone, a protein can have stable;
• one transmembrane α helical domain: Single-pass
• or multiple transmembrane α helical domains: Multiple-pass
2.β-barrel – hydrogen bonding requirements are satisfied …
• single β-strand/multi-stranded β-sheets are unstable
• multipass closed β-barrel like structures are stable

7. Single pass α helix
Membrane Asymmetry…. different
domains on both sides
α helix could be glycosylated but on
extracellular side
Disulfide bonds also formed on
extracellular side
Figure 10-27. A typical single-pass
transmembrane protein.
Note that the polypeptide chain traverses lipid
bilayer as a right-handed α-helix and that
oligosaccharide chains and disulfide bonds are
all on non-cytosolic surface of membrane.
Disulfide bonds do not form between sulfhydryl
groups in cytoplasmic domain of protein
because the reducing environment in the cytosol
maintains these groups in their reduced (-SH)
form.

8. Multi-pass Integral Membrane Proteins
α helical
β-barrel

9. Integral or Intrinsic Membrane Proteins
Penetrate the lipid bi-layer
• Transmembrane proteins
• Amphipathic
• Domain within the membrane – hydrophobic
• Domains projecting from the lipid bi-layer – hydrophilic
• Firmly bind to membrane by hydrophobic interactions
• Not fixed and may move across the membrane
• Solubilized with detergents
• Most have one or more membrane spanning domains (e.g. α-helix)

10. Integral membrane proteins are amphiphilic with
specific domains
70-80% membrane proteins are integral….. Include
 Antigenic proteins
 Transport proteins
 Drug and hormone receptors
 Receptors for lectins & antibodies
Integral proteins have domains that extend into hydrocarbon
core of membrane
 Intra-membrane domains have largely hydrophobic residues,
that interact with membrane lipids
 parts extending into aqueous environment have largely
polar surface residues

11. Membrane-spanning α-helix is most common
structural motif found in integral proteins
In an α-helix, amino acid R-groups
protrude out from helix backbone
Hydrophobic R-groups of a membrane-
spanning α-helix contact hydrophobic
membrane core
Polar peptide backbone is buried
At ends polar groups make ionic
interactions with polar head groups of
phospholipids

12. • Lysine & arginine are often at the lipid/water interface
• Positively charged groups at the ends of their aliphatic
side chains extend toward the polar membrane surface.
• Tyrosine and tryptophan are common near membrane surface.
• Polar character of tryptophan amide group and tyrosine
hydroxyl, along with hydrophobic ring structures, suit for
localization at polar/apolar interface
Particular amino acids tend to occur at different positions relative to
the surface or interior of the bilayer in transmembrane segments of
integral proteins.
Residues with aliphatic side-chains (leucine, isoleucine,
alanine, valine) predominate in the middle of the bilayer
• Cys, Thr and Ser can H bond to the main chains
• Pro and Gly are more common in membrane helices
than in soluble protein helices.

13. Figure 10-21 Molecular Biology of the Cell (© Garland Science 2008)
Only α-carbon backbone of polypeptide chain is shown,
with hydrophobic amino acids in green & yellow.
(J. Deisenhofer et al., Nature 318:618-624 and
H. Michel et al., EMBO J. 5:1149-1158)
Hydrophobic R-chains are involved in;
- van der Waals interactions with fatty chains
- shield all H-bonded polar C=O & NH

14. Figure 10-25 Molecular Biology of the Cell (© Garland Science 2008)
• Sequence of hydrophobic amino acids of a membrane protein can contain
information that mediates protein-protein interactions.
• Individual transmembrane segments of a multipass membrane protein occupy
defined positions in the folded protein structure determined by interactions
between neighboring transmembrane α helices.
Helices of single pass membrane
proteins often associate with each other

15. Figure 10-24 Molecular Biology of the Cell (©
Garland Science 2008)
• Cytosolic or noncytosolic loops of multipass
transmembrane protein segments can be clipped
with proteases and resulting fragments stay
together and function normally.
• In some cases, separate pieces can be expressed
in cells and they assemble properly to form a
functional protein
Helices of multi-pass proteins occupy
defined positions in final structure

16. Best quoted example: Glycophorin
• Erythrocyte membrane’s Major sialoglycoprotein existing as homo-dimer.
• Composed of 60% carbohydrate including sialic acid and 40% protein.
• N- terminus in on extracellular side (glycosylated) & C- terminus cytosolic side.
• Residues 62–95 are buried in the membrane [73 - 95 form an α helix]
• C-terminus rich in charged and uncharged polar residues.
• Involved in different biological activities like;
- binding of MN blood groups
- influenza viruses
- kidney bean phytohemagglutinin, and wheat germ agglutinin
• α helix composed entirely of hydrophobic (or uncharged) amino acids.
• Predicted length of α helix: 3.75 nm….
Helix Retention: Hydrophobic helix is prevented from slipping across membrane by
a flanking set of +vely charged amino acids (lysine and arginine) …… interact
with negatively charged phospholipid head groups.

17. Figure 3-33. Amino acid sequence and
transmembrane disposition of glycophorin A
from the erythrocyte plasma membrane. The
ionic interactions shown between positively
charged arginine and lysine residues and
negatively charged phospholipid head groups in
the cytosolic and exoplasmic faces of the
membrane are hypothetical. [See V. T. Marchesi,
H. Furthmayr, and M. Tomita, 1976, Ann. Rev.
Biochem. 45:667; A. H. Ross et al., 1982, J. Biol.
Chem. 257:4152.]

18. Glycophorin dimer

19. • One of the best characterized integral membrane proteins
• From Halobacter halobium – grows best at 4.3 M NaCl
• Under low O2 conditions…. Gets 0.5 μm wide patches of purple membrane
• Only protein is bacteriorhodopsin
• 247 residue long light-driven proton pump
• Light absorbing element is retinal covalently bound to Lys216
• Structure resolved with electron crystallography
• Bundle of seven 25-residue α-helices spanning membrane in perpendicular
direction
• Adjacent helices are connected head to tail by short loops
• Charged residues are near surfaces of membrane, in contact with aqueous
solvent
• Internal charged residues line center of helix bundle – ……..
form hydrophilic channel for protons
Bacteriorhodopsin
Part of a solar energy transducer provides energy to
bacterial cell

20. Figure 10-32 Molecular Biology of the Cell (© Garland Science 2008)

21. Figure 3-34. Overall structure of bacteriorhodopsin
[Adapted from R. Henderson et al., 1990, J. Mol. Biol. 213:899
Figure 12.19. Amino Acid Sequence of Bacteriorhodopsin.
The seven helical regions are highlighted in yellow and the charged residues in red

22. Bacteriorhodopsin is a light-driven proton pump
• Retinal molecule is covalently linked to Lys216 of protein
• Retinal changes conformation from trans to cis by absorbing a photon, also
causing conformational change in protein
• Photo-isomerization of retinal (from trans to cis) generates proton pump
• Asp85 accepts a proton from retinal & releases into extracellular side (EC)
• Re-protonation of retinal by Asp96 restores its trans isomerized form
• This results in a second proton being released to the EC side
• Asp85 releases its proton where a new cycle may begin
Mechanism of Primary Proton Transfer in Bacteriorhodopsin
(2004). Structure. 12(7): 1281–1288

23. 3 H+
transfers are thought to complete cycle
From cytosol Asp 96
From Asp 96 chromophore Asp 85
From Asp 85 extra-cellular space
Single photon of light excites chromophore
Conformational changes in protein
Protein pumps protons from cytosol
across bacterial membrane
extracellular space
H+
concentration gradient generated across
membrane
Proton gradient used to synthesize ATP
Mechanism of Proton Pump

24. Membrane Proteins Often Function as Large
Complexes
• Some membrane proteins function as part of multi-component
complexes.
• A few of have been studied by x-ray crystallography.
• Bacterial photosynthetic reaction center, first transmembrane protein
complex to be crystallized and analyzed by x-ray diffraction.
• Results of this analysis were of general importance to membrane biology
because they showed for the first time how multiple polypeptides
associate in a membrane to form a complex protein machine.
• Membrane proteins are often arranged in large complexes;
- for harvesting various forms of energy
- for transducing extracellular signals into intracellular ones

25. Bacterial Photosynthetic Reaction Center (PRC)
• comprises four subunits and several prosthetic groups,
including four chlorophyll molecules.
• In this complex protein
- three of the four subunits span membrane
- two subunits (L and M) contain five membrane-spanning α helices
1187 residue photosynthetic reaction center of Rhodopseudomonas
viridis was the first transmembrane protein described in atomic detail
11 α helices form a 45 Å cylinder with hydrophobic surface
Complex consists of four subunits, L, M, H, and a cytochrome
Structure determined by x-ray diffraction analysis of crystals

26. (Adapted from a drawing by J. Richardson based on
data from J. Deisenhofer et al., Nature 318:618-624)
Figure 10-34 Molecular Biology of the Cell (© Garland Science 2008)
The three-dimensional structure of
photosynthetic reaction center of
bacterium Rhodopseudomonas viridis.
L and M subunits form core of reaction center
Each contains five a helices that span lipid bilayer
Locations of various electron carrier
coenzymes are shown in black

27. A family of bacterial outer envelope channel proteins called porins have instead
β barrel structures.
Much of porin primary structure consists of alternating
polar & non-polar amino acids
• Polar residues face aqueous lumen
• Non-polar residues contact membrane lipids
Multiple β Strands in Porins Form Membrane-Spanning
“Barrels”
Porins are channel-forming proteins, usually
trimers of identical 30-50 kDa subuntis
Each subunit 16 β stranded forms a barrel-
shaped structure with a pore in center
Porins allow solutes <600 daltons to pass
Porins – largely restricted to;
- bacterial outer membranes and
- outer membranes of mitochondria and chloroplast
Smaller β barrels function as receptors or anchored enzymes

28. Gram –ive Bacteria and Porins
• Figure 11-17. A small section of the double membrane of an E. coli bacterium
Several types of porin found in outer membrane of gram-negative bacteria E. coli
Outer membrane;
- protects an intestinal bacterium from harmful agents
e.g., antibiotics, bile salts, and proteases
- permits uptake & disposal of small hydrophilic molecules, nutrients & wastes
Porins in outer membrane of an E. coli cell provide channels for passage of
disaccharides, phosphate, and similar molecules

29. Figure 10-32. The three-dimensional structure of a porin trimer of
Rhodobacter capsulatus determined by x-ray crystallography
(B) Monomers tightly associate to form trimers,
which have three separate channels for diffusion
of small solutes through the bacterial outer
membrane. A long loop of polypeptide chain
(shown in red), which connects two b strands,
protrudes into the lumen of each channel,
narrowing it to a cross-section of 0.6 x 1 nm.
(A) Each monomer consists of a 16-stranded
antiparallel b barrel that forms a
transmembrane water-filled channel.
(Adapted from M.S. Weiss et al., FEBS
Lett.280: 379-382)

30. Figure 12.21. Amino Acid Sequence of a Porin
Some membrane proteins such as porins are built from β strands that tend to have
hydrophobic and hydrophilic amino acids in adjacent positions. The secondary
structure of Rhodopseudomonas blastica is shown, with the diagonal lines
indicating direction of H-bonding along the β sheet. Hydrophobic residues (F, I, L,
M, V, W, and Y) are shown in yellow. These residues tend to lie on the outside of
the structure, in contact with the hydrophobic core of the membrane.

32. Figure 10-21. β barrels formed from different numbers of β strands
(1) E. coli OmpA protein (8 β strands), which serves as a receptor for a bacterial virus.
(2) E. coli OMPLA protein (12 β strands), is a lipase that hydrolyses lipid molecules. The amino
acids that catalyze enzymatic reaction (shown in red) protrude from outside surface of barrel.
(3) A porin from bacterium Rhodobacter capsulatus, which forms water-filled pores across outer
membrane (16 β strands). Diameter of channel is restricted by loops (shown in blue).
(4) E. coli FepA protein (22 β strands), which transports iron ions.
The inside of the barrel is completely filled by a globular protein domain (shown in blue) that
contains an iron-binding site.
This domain is thought to change its conformation to transport
bound iron, but the molecular details of the changes are not known.

33. Integral Monotopic Proteins
are permanently attached to lipid membrane from only one
side and do not span across the whole bilayer
Examples:
- prostaglandin H2 synthases 1 and 2 (cyclooxygenases)
- lanosterol synthase and squalene-hopene cyclase
- microsomal prostaglandin E synthase
- carnitine O-palmitoyltransferase 2

35. Proteins without a full transmembrane domain can be anchored to
membrane by an amphipathic α helix
Figure 12.23. Attachment of Prostaglandin
H2
Synthase-1 to the Membrane. Prostaglandin
H2
synthase-1 is held in membrane by a set of α
helices coated with hydrophobic side chains. One
monomer of the dimeric enzyme is shown
Figure 12.24. HYdrophobic Channel of
Prostaglandin H2
Synthase. A view of
prostaglandin H2
synthase from the membrane,
showing the hydrophobic channel that leads to
the active site. The membrane-anchoring helices
are shown in orange.
-e.g. prostaglandin H2 synthase-1 are integral membrane enzymes firmly
bound to membrane by a set of α helices
- Catalyze conversion of arachidonic acid into prostaglandin H2
- PH2 promotes inflammation and modulates gastric acid secretion

36. Attach covalently to membranes via lipid anchors;
- Fatty acid (e.g., palmitate or myristate)
- Isoprenoid group
- Phospholipid
Protein attachment/orientation could be;
- Cytosolic
- Extra-cytosolic
Lipid-anchored membrane proteins

37. Fatty Acyl Anchors
Myristoylation: C14 myristoyl
• occurs co-translationally
• Stable linkage
• amide linkage to N-terminal Gly
Palmitoylation: C16 palmitoyl
• occurs posttranslationally
• is reversible
• Linkage via thioester/ester to Cys/Ser
Figure 10-20 Molecular Biology of the
Cell (© Garland Science 2008)

38. Isoprenoid Anchor
1. Farnesyl C15
2. Geranylgeranyl C20
Attach via a thioether linkage to a cysteine thiol
Need Signal Sequence:
Cys-aliphatic-aliphatic-X- C terminus
• Prenyl group added to Cys four residues away from
carboxyl terminus
• Terminal 3 residues…aliphatic-aliphatic-X removed
X = Leu in geranylgeranyl anchor
X = Ala/Met/Ser in farnesyl anchor
• Cys is methyl esterified before insertion into
membrane
• prenylated proteins often move between cytosol and
membrane

39. Thio-ether
linkages
Amide
linkage
Thio-etser
linkage
Comparison of Lipid
Anchors & Linkages
Used to Attach
Membrane Proteins

40. GPI Anchor
Glycosylphosphatidylinositol (GPI) groups – anchor a wide variety of proteins
to exterior surface of plasma membrane
• Phosphatidylinositol is glycosidically linked to a linear tetrasaccharide
• Mannose forms phosphoester bond with phosphoethanolamine
• PE is amide linked to COOH-terminus of protein
GPI groups are attached in RER soon after translation is done
Proteins contain a signal sequence which is;
– a C-terminal 20 to 30 hydrophobic residues long stretch
– removed when GPI anchor is added to protein
GPI-anchored proteins exit ER in vesicles separate from other secretory cargo
Glycosylphosphatidylinositol anchor: C-terminal α-carboxyl of
protein-phosphoethanolamineglycan- phosphatidylinositol

41. GPI linkage oligosaccharide composition
may vary
Protein (C-term.) -
phosphoethanolamine – mannose -
mannose - mannose –
N- acetylglucosamine –
Inositol of PI in membrane

42. Why lipid anchors?
N-terminal FA anchors
• N-terminal anchor is necessary for retention at membrane
• may play an important role in a membrane-associated function
e.g….. v-Src, mutant form of a cellular tyrosine kinase, is oncogenic &
can transform cells only when it retains a myristylated N-terminus
GPI anchor
• Several hydrolases like alkaline phosphatase, fall into this class
• phospholipid anchor is shown to be both necessary and sufficient for
binding cell-surface proteins to membrane
Like enzyme phospholipase C cleaves phosphate-glycerol bond in
- phospholipids &
- glycosylphosphatidylinositol anchors

43. A Prenyl Protein Protease a New Chemotherapy
Target
Protein called p21ras or simply Ras is a small GTP-binding
protein involved in cell signaling pathways that regulate
growth and cell division
Mutant forms of Ras cause uncontrolled cell growth, and Ras mutations are
involved in one third of all human cancers
WHY?
Because signaling activity of Ras is dependent on prenylation as well as
• proteolysis of the -AAX motif and
• methylation of prenylated Cys residue
been considered targets for development of new chemotherapy strategies
• Mutations inhibiting prenyl transferases cause defective growth or death
of cells
Ras Protein Farnesyltransferase: A Strategic Target for
Anticancer Therapeutic Development. Journal of Clinical
Oncology (JCO) November 1999 vol. 17no. 11 3631-3652

44. Table 2. Mammalian CAAX Proteins That Are Known or Likely to Be
Prenylated
CAAX Protein(s) Function(s)
Farnesylated
H-Ras, K4B-Ras, and N-Ras Signaling for growth, differentiation, apoptosis
Lamins A and B Nuclear membrane structure
Rho-B and Rho-E Cytoskeletal organization; gene expression; cell cycle control
Pxf Peroxisomal location
Phosphorylase kinase α and
β
Skeletal muscle function
Inositol-1,4,5-triphosphate Lipid phosphatase; calcium signaling
5-phosphatase type I
CAAX Protein(s) Function(s)
Geranylgeranylated
G-proteins γ-subunits Signaling for growth, differentiation, apoptosis
Rho A, B, C, and G Cytoskeletal organization; gene expression; cell
cycle control
Cdc42 Rho family; cytoskeletal organization; cell polarity
in Saccharomyces cerevisiae
Rac 1 and 2 Membrane ruffling; actin reorganization
Inositol-1,4,5-triphosphate 5-phosphatase
type I
Lipid phosphatase, calcium signaling

46. Figure 1. Prenyl Function Inhibitors.
Chen M, Knifley T, Subramanian T, Spielmann HP, et al. (2014) Use of Synthetic Isoprenoids
to Target Protein Prenylation and Rho GTPases in Breast Cancer
Invasion.
PLoS ONE 9(2): e89892. doi:10.1371/journal.pone.0089892
Potential anti-cancer
therapeutics
Prenyl Function Inhibitors (PFIs)
Farnesol or geranyl-geraniol
analogs act as alternate substrates
for FTase or GGTase;
- Anilinogeraniol (AGOH) and
- Anilinofarnesol (AFOH)
block invasion of breast cancer
cells

47. Figure 8. AFOH blocks 3D invasive growth of MDA-MB-231 cells.
Chen M, Knifley T, Subramanian T, Spielmann HP, et al. (2014) Use of Synthetic Isoprenoids to Target Protein Prenylation and Rho
GTPases in Breast Cancer Invasion. PLoS ONE 9(2): e89892. doi:10.1371/journal.pone.0089892
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0089892

48. Categories of peripheral proteins
Cytoskeletal Proteins
HELP IN MAINTAINING CELL SHAPe and anchoring soluble proteins to
membrane e.g. spectrin and actin in erythrocytes
Peripheral proteins contain a wide range of proteins with varied functions;
Enzymes
An important group of peripheral membrane proteins are water-soluble enzymes
that associate with the polar head groups of membrane phospholipids.
Protein kinases, phosphatases etc.
…. bacterial, fungal, gastric and pancreatic
- Lipases/ phospholipases
- Palmitoyl protein thioesterases, and
- Cholinesterases
One well-understood phospholipase C from erythrocytes
- Hydrolyzes various bonds in the head groups of phospholipids.
- Has an important role in degradation of damaged or aged cell membranes.

49. Transporters of small hydrophobic molecules
• Proteins function as carriers of non-polar compounds between
different types of cell membranes or between membranes and
cytosolic protein complexes.
• Transported substances are phosphatidylinositol, tocopherol,
gangliosides, glycolipids, sterol derivatives, retinol, or fatty acids.
 Glycolipid transfer proteins
 Lipocalins including retinol binding proteins and fatty acid-
binding proteins
 Polyisoprenoid-binding protein
 Ganglioside GM2 activator proteins
 Sterol carrier proteins
Electron carriers
Proteins are involved in electron transport chains
Cytochrome c
Cupredoxins
Adrenodoxin reductase
some flavoproteins etc

50. Polypeptide hormones, toxins, and antimicrobial
peptides
• Many hormones, toxins, inhibitors, or antimicrobial peptides interact
specifically with transmembrane protein complexes.
• They can also accumulate at the lipid bilayer surface, prior to
binding their protein targets.
• Such polypeptide ligands are often positively charged and interact
electrostatically with target transmembrane proteins….
o Alpha lact-albumin from mammary gland
o Aldolase erythrocyte membrane
o Scorpion venom
o Snake venom
o Botulinum toxin B
o Heat-stable enterotoxin

51. Movements of Membrane Proteins in the Plane
of Membrane
Many Membrane Proteins Diffuse in the Plane of Membrane
Types of movements membrane proteins undergo are;
• Rotational diffusion: rotate about an axis perpendicular to the
plane of bilayer
• Lateral diffusion: move laterally within the membrane
Membrane proteins do not flip-flop across lipid bilayer
First direct evidence that some plasma membrane proteins
are mobile in the plane of membrane was provided by hybrid
cells (heterocaryons).

52. Membrane proteins of intercellular junctions cannot be allowed to diffuse
laterally in the interacting membranes
• In epithelial cells (lining gut or kidney tubules) enzymes and transport
proteins are confined to apical, basal, lateral surfaces of cell
• Often essential for the function of epithelium
A cell can also create membrane domains without using intercellular
junctions
• Plasma membrane of nerve cells, for example, contains;
- a domain enclosing cell body and dendrites and another
- enclosing the axon (a belt of actin filaments tightly associated with the
plasma membrane at the cell-body-axon junction forms part of the barrier
Cells Can Confine Proteins and Lipids to Specific Domains Within
a Membrane
Cells are known to have a variety of ways of immobilizing
membrane proteins
Formation of large aggregates: individual protein molecules are relatively
fixed in relationship to one another & diffuse very slowly
Tethering to macromolecular assemblies either inside or outside the cell
e.g. membrane proteins are anchored to the cytoskeleton inside

53. Four ways in which lateral mobility of specific plasma membrane
proteins can be restricted
Figure 10-39 Molecular Biology of the Cell (© Garland Science 2008)
Self-assembly
Tethered to macromolecules outside
Tethered to macromolecules inside
Cell-cell adhesion

54. Proteins Restrictions
Tight Junction is one kind of them
Proteins & lipids on outer layers can’t move to other
compartments
Figure 10-37 Molecular Biology of the Cell (© Garland Science 2008)

55. Tom Kirchhausen. Bending
membranes. Nature Cell
Biology 14, 906–908 (2012)
Figure 1: Mechanisms to
generate membrane curvature
Mechanisms by which proteins can generate
membrane curvature