Membrane Receptor, Membrane

Structure and Transport

Membrane models
Membrane proteins & Membrane carbohydrates
Chemical signals, Cellular receptors, G-protein receptors, Protein kinase receptors
Membrane transport: Permeability of the lipid bilayer, Diffusion and osmosis
Types of proteins in passive and active transport

By Dr Gan Sook Yee

Bachelor of Science (Hons) Chinese Medicine
 The development of the Fluid Mosaic Model
Overton (1890s) Lipids are important components
of membranes
Langmuir (1900s) Lipid Monolayer
Gorter & grendel The basis of membrane Structure
(1925) is a lipid bilayer
Davson & Danielli Membranes also contain proteins
(1935) (protein-lipid-protein sandwich)

Robertson All membranes share a common

(1950s) underlying structure (Unit
membrane)
Singer & Nicolson Fluid Mosaic Model (membrane
(1972) consists of a mosaic of proteins in
a fluid lipid bilayer)
Unwin &Henderson Membrane protein Structure
(1975s) (Some membrane proteins contain
transmembrane segments)
 Plasma Membrane
A fluid mosaic of phospholipids with proteins and other molecules
embedded in a phospholipid bilayer.
 Most of the lipid is phospholipid.
Phospholipids (amphipathic)
* hydrophillic and hydrophobic
Phospholipid arrangement in cell membranes
-a bilayer
- hydrophobic tails pointing inwards, away from both inside and outside the cell

Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

Membrane is asymmetric (The two sides are different)
(1)Proteins are inserted uni-directionally

The same side facing either in or out.

They transport molecules or ions from one side to the other
in a specific direction.

Receptors face in the same direction because the
molecules they are designed to recognize only come from
one direction.

(2) Different kinds of lipids present and different degree of

unsaturation of fatty acids
 Membrane Proteins
Intrinsic proteins – trans-membrane spanning

Extrinsic (peripheral) proteins – confined to inner or outer surface

Intrinsic proteins
• Some act as carrier molecules to transport substances.
• Membrane Protein ATP

(a) Transport proteins (facilitate the movement of nutrients such as sugars and
amino acids across membranes)
(b) Channel proteins (provide hydrophilic passageways through hydrophobic
membranes)
(c) Transport ATPase (use the energy of ATP to pump ions across membranes)

• Other intrinsic proteins – termed enzymes which catalyse specific metabolic

reactions at a particular location in the cell.
Extrinsic (peripheral) proteins – confined to inner or outer surface
• Many extrinsic proteins combine with carbohydrate groups to form
glycoproteins.
• Act along with glycolipids (lipid molecules joined to a carbohydrate group) as
the chemical receptors of the cell.
 Membrane Carbohydrates
• Face away from cytoplasm (on outside of cell)
• Attached to protein or lipid
– Glycolipids - bound to lipids (blood antigen-determine blood group)
– Glycoproteins - Protein Receptors
– Provide specificity for cell-cell or cell-protein interactions
Serve as loci for specific functions

Molecules and structures responsible for those functions are either
embedded in or localized on membranes

Enzymes as markers during isolation of organelles

Enzymatic Activity
A protein built into the membrane may be an
enzyme with its active site exposed to substances
in the adjacent solution (Several enzymes in team)

 Acid phosphatase activity - determination of the

distribution of lysosomes among various isolated
fractions
Cell to cell Communication and Connection

Cell- cell recognition

Some glycoproteins serve as identification tags that
are specifically recognized by other cells

Intercellular Joining
Membrane proteins of adjacent cells may be
hooked together in various kinds of junctions
 Four types of Connection

• Desmosomes
• Tight junctions Animal cells
• Gap junctions
• plasmodesmata
Tight junctions

Anchoring junction

Gap junctions

Extracellular matrix
Space between cells
Plasma membranes of adjacent cells
Protein strands hold
cells together

Tightly link adjacent cells but permit materials to move in the

intercellular space
 wikimedia.org/wikipedia

Tight junctions formed by strands of protein seal cells together- prevent leakage
Pairs of channels connect insides of adjacent cells
Openings in the walls of adjacent plant cells (cytoplasmic bridges)
Mechanisms for Crossing the Membrane Barrier
In passive transport, substances diffuse through membranes
without energy from areas of high concentration to areas of
low concentration.
• Kinetic energy drives passive transport.
• Transport is dictated by concentration gradient or by both concentration
gradient and electric potential (electrochemical gradient).
Molecules of dye Membrane Equilibrium

Equilibrium

Diffusion evens out the concentrations

(maximum entropy)
 The rate of diffusion
The rate of diffusion in a given direction across the exchange surface:
- is proportional to the area of the surface
- is directly proportional to the concentration gradient
- is inversely proportional to the distance (the length of the diffusion
pathway)
This is known as Fick’s law
 Rate of diffusion is proportional to
Surface area x difference in concentration
length of diffusion path

 Increasing surface area and/or conc.  faster diffusion

 Increasing length of path  slower diffusion
 Rate of diffusion
Factors
• Concentration gradient
• Size of molecule
• Temperature
• Solubility of the molecule
• Surface area of the membrane

Saturation does not occur with simple diffusion or with channel

diffusion
The bigger the gradient, the greater the transport of materials
 Facilitated diffusion
• Molecules that are not soluble in lipids pass through the
phospholipid bilayer by facilitated diffusion.
 glucose, nucleic acids and proteins
• This is a passive process, down a concentration gradient that relies
upon the involvement of specialised carrier proteins.
 Carrier Proteins change conformation during transport

• When a carrier protein transports a single solute across the

membrane (Uniport)
• When two solutes are transported simultaneously (co-transport)
Symport Antiport
Carrier Proteins
 Transport rate reaches a maximum when all protein
transporters are being used (saturation)
 Very specific

 Sensitive to inhibitors that react with protein side

chains
• Cells Regulate Permeability by Adding & Removing Membrane
Transport Proteins
• Stored in vesicles & down-regulated IF not needed
• Hormones regulate membrane transport in this way
 Movement of water (Osmosis)
• A special case of passive transport.
• Osmosis = movement of water from low osmotic pressure
(dilute solution) to high osmotic pressure (concentrated
solution). Equal
Lower Higher concentration
concentration concentration of solute
of solute of solute

H2O
Solute
molecule

Selectively
permeable
membrane

Water
molecule

Solute molecule with

cluster of water molecules

Net flow of water

 Water potential
• Pressure exerted by freely moving water molecules in a system is called the
water potential, measured in kilopascals (kPa).

• The water potential of pure water is given the value of 0kPa.

• The water potential of a solution falls when solutes are added  water
molecules cluster around the solute molecules (solute potential)

• Solute potential is always negative (more –ve as more solutes added).

• The water potential of a plant cell is affected by both the pressure of the cell
wall against the cellular contents (potential pressure) and the solute potential
of the cell.

• Water potential (ψ) = solute potential (ψ) + pressure potential

• Animal cell - determined by its solute potential, effect of cell membrane so

small it is usually ignored.
Water balance between cells and their surroundings is
crucial to organisms
– Osmosis causes cells to shrink in hypertonic
solutions and swell in hypotonic solutions.
– In isotonic solutions, animal cells are normal, but
plant cells are limp.
Isotonic solution Hypotonic solution Hypertonic solution

H2O
H2O H2O H2O

Animal
cell

(1) Normal (2) Lysed (3) Shriveled

H2O Plasma
H2O H2O H2O
membrane

Plant
cell

(6) Shriveled
(4) Flaccid (5) Turgid (plasmolyzed)

– The control of water balance is called osmoregulation.

Cells expend energy for active transport
– Transport proteins can move solutes against a
concentration gradient through active transport,
which requires ATP
Maintain internal concentrations of small molecules of
cells exposed to different surrounding environment

Transport
protein

P P
ATP P Protein Phosphate
Solute ADP changes shape detaches
 There are two types of active transport

Direct Active Transport (Primary Active

Transport)
Accumulation of ions is coupled
directly to hydrolysis of ATP
Involves transport ATPases or ATPase
pumps (Four Types)
 • Maintains Low Na+
and high K+
concentrations in
animal cells
• Pumps 3 (Na+) out for
every 2 (K+) pumped in
• Requires the
hydrolysis of ATP to
ADP
Functions
• Establish an
electrochemical
gradient for secondary
active transport
• Nerve transmission
• Maintenance of
osmotic pressure in
cells
(P: Phosphorylation)

– Inhibited by drugs such as digitalis

 Pump protons (H+) into organelles
(vacuoles, vesicles, lysosomes,
endosomes, the Golgi apparatus,
secretory granules and plant cell
vacuole).

The V-ATPases are multisubunit complexes composed of two

domains. The peripheral V1 domain carries out ATP hydrolysis
while the integral V0 domain is responsible for proton
translocation.
Found in bacteria, mitochondria, chloroplasts
Involve in proton transport
Use the energy of ATP hydrolysis to pump protons
against the their electrochemical potential
OR
Reverse process - the transport of proton down the
gradient is use to drive ATP synthesis (these
proteins are more appropriately called ATP
synthases)
The other three classes of ATPases transport only
cations, the ABC-type ATPases transport a variety of
solutes (ions, sugars, amino acids, peptides and
polysaccharides)
Some pumps antibiotics or drugs out of the cell (cell
resistant) such as multi-drug resistance (MDR)
transport protein
 Chemical signals and cellular receptors
 A chemical messenger/signal is any compound that serves to
transmit a message (usually hormones, neurotransmitters,
cytokines, growth factors or cell recognition molecules).

 They attach to the receptor, triggering changes in the function of the

cell via signal transduction (receptor→ transducer→ effector)

 Receptors perceive the signal, transducers relay the signal and the
effectors convert the signal into an intracellular response.

 Membrane or transmembrane receptors are specialized integral

membrane proteins.

 Often, the effector involves enzymes which are typically protein

kinases and protein phosphatases.
 MODES OF COMMUNICATION & SIGNALING

Direct communication between

adjacent cells through gap
junctions

Autocrine & paracrine signaling

(chemicals that act locally & are
rapidly destroyed)

Neurotransmitters
Nervous signaling involves the rapid
transmission of action potentials &
the release of a neurotransmitter at
a synapse.

Hormones produced by
endocrine & nerve cells
Receptors involved in transmembrane signaling processes:

(1) The G-protein-coupled receptors

• Integral membrane protein with an extracellular recognition site for
ligands and an intracellular recognition site for a GTP-binding protein

(2) The single-transmembrane segment (1-TMS) catalytic receptors

• The extracellular domain has the ligand recognition site while the
intracellular catalytic domain is either a tyrosine kinase or a guanylyl
cyclase

(3) Oligomeric ion channels

• Ligand-gated ion channels
• Ligands are neurotransmitters
 (1) The G-protein-coupled receptors

A protein bound to this receptor on inside surface (cytosolic) is called G

proteins.

• Their characteristic
structure
comprises:
– Seven
transmembrane
spanning helices,
– With an extra-
cellular N-terminal
domain &
– An intra-cellular C-
terminal domain.
 Signal transduction - G protein

• When the ligand binds, the

receptor activates a G
protein by causing the Gα
to release GDP and acquire
GTP.
• The Gα and Gβϒ (the two
subunits always bind
together) then separate
and depending on the G
protein and cell type,
either the GTP-Gα or Gβϒ
will initiate signal
transduction events by
binding to an enzyme or
other proteins in the cell.
• The GTP-Gα eventually
hydrolyzes its bound GTP
and becomes inactive
GDP-Gα which combine
with Gβϒ to form inactive
heterotrimeric G protein.
 (2) The single-transmembrane segment (1-TMS) catalytic receptors:
Receptor tyrosine kinases

• The transmembrane segment is of course a α−helix. On either side of this

membrane spanning helix are globular domains (extra-cellular ligand binding
domain & intracellular catalytic domain).

• The signaling molecule binds to the binding site and causes a conformational
change on the catalytic function which results in autophosphorylation (receptor
phosphorylates its own tyrosine groups).

• Phosphotyrosines serve as “docking” sites for cytoplasmic proteins, leading to a

cascade of signaling pathways within the cell

– Two important pathways:

• Ras/Raf/MAP kinase pathway – cell division, growth and differentiation
• Jak/Stat pathway – activated by cytokines, involved in synthesis and
release of inflammatory mediators
 α

Three classes of receptor tyrosine kinases:

Class 1 (ex. epidermal growth factor (EGF) receptor-extracellular domain contains two
Cys-rich repeat.
Class II (ex. Insulin receptor) - α2β2 tetramer with transmembrane β and Cys-rich
extracellular α.
Class III (ex. Platelet-derived growth factor (PDGF) receptor) have 3/5
immunoglobulin-like extracellular domains.
(1-2) Signal transduction initiated by binding of ligand, causing receptor to
aggregate or cluster together.
(3) Tyrosine kinase associated with each receptor phosphorylates the tyrosines
of neighbouring receptors (autophosphorylation-phosphorylate other receptor of
the same type).
(4)Receptor recruits a number of cytosolic proteins to interact with itself.