Membrane Proteins Flashcards
Fluid mosaic model
The plasma membrane
consists mainly of a fluid
mosaic bilayer of
phospholipids and
protein.
* Phospholipids will
naturally form bilayers in
aqueous environments
* Hydrophilic head groups
align to the extracellular
space or cytoplasm, and
the hydrophobic tails
point inwards.
How are integral proteins held within the membrane?
Regions of hydrophobic R groups allow strong hydrophobic interactions that hold integral
membrane proteins within the phospholipid bilayer
The phospholipid bilayer is a barrier to…
ions and most uncharged polar molecules. Some small molecules, such as oxygen and carbon dioxide, pass through the bilayer by
simple diffusion
Some integral proteins are also
transmembrane proteins
Peripheral proteins
Hydrophilic proteins bound to the surface of membranes mainly by ionic and hydrogen interactions.
Facilitated diffusion
the passive transport of substances across the membrane through specific transmembrane proteins
Ligand-gated channels
controlled by the binding of signal molecules
voltage-gated channels
controlled by changes in ion concentration
Transporter proteins
bind to the specific substance to be transported and undergo a
conformational change to transfer the solute across the membrane
requirement for active transport
A source of metabolic energy
How is energy provided for conformational changes?
Some active transport proteins hydrolyse ATP directly to provide the energy for the
conformational change required to move substances across the membrane
formation of the electrochemical gradient
For a solute carrying a net charge, the concentration gradient and the electrical potential
difference combine. This determines the transport of the solute
Ion pumps use energy from
the hydrolysis of ATP to
establish and maintain ion gradients
The sodium-potassium pump process
The pump has high affinity for sodium ions inside the cell; binding occurs; phosphorylation
by ATP; conformation changes; affinity for sodium ions decreases; sodium ions released
outside of the cell; potassium ions bind outside the cell; dephosphorylation; conformation
changes; potassium ions taken into cell; affinity returns to star
The sodium potassium pump and the small intestine
in the small intestine, the sodium gradient created by the sodium-potassium pump drives
the active transport of glucose
The glucose transporter responsible for this glucose symport transports sodium ions and
glucose at the same time and in the same direction
Binding changes the conformation of the receptor, which
initiates a response within the cell
Hydrophobic signalling molecules
can diffuse directly through the phospholipid bilayers of
membranes, and so bind to intracellular receptors
transcription factors
The receptors for hydrophobic signalling molecules
examples of hydrophobic signalling
molecules
steroid hormones oestrogen and testosterone
Steroid hormones bind to specific receptors in..
the cytosol or the nucleus
The hormone-receptor complex moves to the nucleus where…
it binds to specific sites on
DNA and affects gene expression
Hydrophilic signalling molecules
bind to transmembrane receptors and do not enter the
cytosol
Transmembrane receptors change conformation when
the ligand binds to the extracellular
face; the signal molecule does not enter the cell, but the signal is transduced across the
plasma membrane
Transmembrane receptors act as signal transducers by
converting the extracellular ligand binding event into intracellular signals, which alters the behaviour of the cell
Phosphorylation cascades
allow more than one intracellular signalling pathway to be
activated
Binding of the peptide hormone insulin to its receptor results in
an intracellular signalling
cascade that triggers recruitment of GLUT4 glucose transporter proteins to the cell
membrane of fat and muscle cells
Diabetes mellitus can be caused by
failure to produce insulin (type 1) or loss of receptor
function (type 2)
What can also recruit GLUT-4 ?
Exercise also triggers recruitment of GLUT4, so can improve uptake of glucose to fat and
muscle cells in subjects with type 2
Resting membrane potential
a state where there is no net flow of ions across the
membrane
The transmission of a nerve impulse requires
changes in the membrane potential of the
neuron’s plasma membrane
action potential
a wave of electrical excitation along a neuron’s plasma membrane
Depolarisation of the plasma membrane
as a result of the entry of positive ions triggers the
opening of voltage-gated sodium channels, and further depolarisation occurs
Restoration of the resting membrane potential
Inactivation of the sodium channels and the opening of potassium channels restores the
resting membrane potential
Depolarisation of a patch of membrane causes
neighbouring regions of membrane to
depolarise and go through the same cycle, as adjacent voltage-gated sodium channels are
opened
When the action potential reaches the end of the neuron…
it causes vesicles containing
neurotransmitter to fuse with the membrane — this releases neurotransmitter, which
stimulates a response in a connecting cell
Restoration of the resting membrane potential allows
the inactive voltage-gated sodium
channels to return to a conformation that allows them to open again in response to
depolarisation of the membrane
Ion concentration gradients are
re-established by the sodium-potassium pump, which
actively transports excess ions in and out of the cell
The cytoskeleton
gives mechanical support and shape to cells
The cytoskeleton consists of…
different protein structures including microtubules, which are found in all eukaryotic cells
Microtubules
control the movement of membrane-bound organelles and chromosomes
Cell division requires
remodelling of the cytoskeleton
Formation and breakdown of microtubules involves
polymerisation and depolymerisation of
tubulin
The cell cycle consists
interphase and mitotic (M) phase
Mitotic phase involves
mitosis and cytokinesis
Mitosis consists of
prophase, metaphase, anaphase and telophase
Progression through the cell cycle is controlled by
checkpoints
Cyclin proteins that accumulate during cell growth are
involved in regulating the cell cycle
G1 checkpoint
retinoblastoma protein (Rb) acts as a tumour suppressor by
inhibiting the transcription of genes that code for proteins needed for DNA replication
Phosphorylation by G1 cyclin-CDK
inhibits the retinoblastoma protein (Rb)
G2 checkpoint
the success of DNA replication and any damage to DNA is assessed
DNA damage triggers
the activation of several proteins including p53 that can stimulate DNA repair, arrest the cell cycle or cause cell death
metaphase checkpoint
controls progression from metaphase to anaphase
An uncontrolled reduction in the rate of the cell cycle may result in
degenerative disease
uncontrolled increase in the rate of the cell cycle may result in
tumour formation
proto-oncogene
a normal gene, usually involved in the control of cell growth or division, which can mutate to form a tumour-promoting oncogene
Apoptosis is triggered
by cell death signals that can be external or internal
External death signal molecules bind to
a surface receptor protein and trigger a protein
cascade within the cytoplasm
An internal death signal resulting from DNA damage causes
activation of p53 tumour-suppressor protein
Both types of death signal result in
the activation of caspases (types of protease enzyme)
that cause the destruction of the cell
Apoptosis is essential during
development of an organism to remove cells no longer
required as development progresses or during metamorphosis
absence of growth factors
Cells may initiate apoptosis
Mitosis phases
Prophase Metapahse Anaphase Telaphase
Prophase
◦ DNA condenses into chromosomes, each of which
consists of two sister chromatids which are joined at
the centromere.
◦ The nuclear membrane breaks down.
◦ Spindle microtubules extend from the MTOC (by
polymerisation) and attach to chromosomes via their
kinetochores (areas where spindle fibres bind) in the
centromere region.
Metaphase
Chromosomes align at the metaphase plate (the equator of the spindle).
Anaphase
◦ Spindle fibres shorten by depolymerisation.
◦ This causes the sister chromatids to become separated
and so the chromosomes are pulled to opposite poles.
◦ Each chromatid can now be called a chromosome.
◦ By the end of anaphase, the two poles of the cell each
have an identical and complete set of chromosomes.
Telophase
◦ The chromosomes decondense (uncoil) and nuclear
membranes form around them.
◦ Cytokinesis also takes place during this period, which
involves the separation of the cytoplasm into two
daughter cells.
Cyclins combine with and activate
cyclin-dependent kinases (CDKs).
Active cyclin-CDK
Active cyclin-CDK complexes will phosphorylate proteins, specifically the proteins which
regulate the progression through the cycle.
the cell cycle is allowed to progress if…
there is sufficient phosphorylation
G1
If an insufficient threshold is reached, the cell is held at a checkpoint.
◦ During this time there is low levels of CDK activity so Rb binds with a transcription factor
preventing the transcription of genes required for entering the S phase.
◦ As CDK activity increases, Rb is repeatedly phosphorylated. Once sufficient phosphorylation
has taken place Rb no longer binds with the transcription factor allowing them to promote the
transcription of genes required for DNA replication in the S phase.
◦ The ‘go ahead’ signal is then given at the G1 checkpoint. (G1S)
G2
During the S phase, DNA should be replicated successfully.
◦ The G2 checkpoint will determine how successfully the DNA has been replicated.
◦ The G2 checkpoint also allows for any damage to DNA to be assessed.
◦ As DNA damage can ultimately lead to cancer, if DNA damage is detected, the activation of
several proteins, such as p53, is triggered.
◦ This can:
◦ stimulate DNA repair
◦ arrest the cycle
◦ cause cell death (apoptosis)
Metaphase checkpoint
A metaphase checkpoint will control the progression from metaphase to anaphase.
◦ Progression will be halted until the chromosomes are aligned correctly on the metaphase
plate and attached to the spindle microtubules.
◦ This ultimately ensures that each cell receives the correct number of chromosomes.
Type 1 diabetes is caused by
insufficient production of insulin
Explain how a single signalling molecule such as testosterone is able to influence the expression of multiple genes.
Each gene will possess hormone response elements/DNA sequences that bind the hormone-receptor
complex/transcription factor.
Name the glucose transporter that enables glucose transport in these
cells.
GLUT-4
