Membrane Structure Flashcards
Membranes are composed of
lipids, carbohydrates, and proteins
Membrane function
physical barriers that define boundaries
Membranes spontaneously form
sealed structures
Proteins that span the membrane control ________
the movement of molecules between the inside and outside of the structure (cell or organelle).
The plasma membrane defines _____
the boundary of the cell and membrane proteins sense the extracellular environment
Organelles are _____
membrane-bound compartments that have specific structures and functions.
Each membrane type has a _____
unique complement of proteins and lipids.
Lipids, which form the primary structure of the membrane, ____
often have carbohydrates attached on the extracellular surface.
Proteins embedded in the membrane also often have _____
carbohydrates attached to the extracellular domains of the protein.
primary component of membrane
lipids
All of organelles are delimited by ______.
membranes:
nucleus, mitochondria, ER, vacuole, Golgi, lysosomes, peroxisomes, and many vesicles.
Internal membrane surface area is ________ than that of plasma membrane.
10 fold greater
All cell membranes are _________.
lipid bilayers (~ 5 nm in thickness) with proteins embedded in or associated with the bilayer
The cytoskeleton (for moving vesicles and organelles and for maintaining shape) occupies over ______ area than the internal membranes.
10 fold more
The enormous surface area of the cytoskeleton allows it to function
as a scaffold on which cellular reactions can take place.
Most ______ substances cannot pass through the bilayer unless a protein enables the passage of the substance.
water soluble
Proteins spanning the lipid bilayer mediate ________
many of the functions of the membrane (~30% of the all proteins encoded in the genome are membrane or membrane-associated proteins).
Lipid bilayers are _____
dynamic and fluid structures; membrane fluidity depends on composition and temperature.
The typical lipid molecule exchanges places with its neighbors in a bilayer ___ times/second and diffuses several mm/second at __°C within a lipid bilayer leaflet.
107
37
Phospholipids do not spontaneously flip-flop in membranes. For specific functions, an _________ catalyzes flip-flop.
an ATP driven Flippase
Carbohydrates on membrane proteins and lipids are exceedingly important for _________.
for development, immunological responses, binding of viruses and toxins, and for proper protein folding.
Carbohydrates are on the _______ side of the plasma membrane
extracellular
If you add energy to a solution of cells or organelles by physically shaking the solution, it is possible to break membranes, but they will ________.
spontaneously reseal
The resealed vesicle is the most energetically favorable state since it avoids ________.
the exposure of the hydrophobic hydrocarbon tails to water
If the cell wants to move proteins from one organelle to another, how does it do this? How does it get membranes to fuse?
The cell uses specialized proteins to pull the membranes into contact with each other
The three classes are:
phospholipids, sphingolipids, and cholesterol
3 classes are all considered: ______ and are synthesized in _______
amphipathic (contain hydrophilic and hydrophobic domains).
ER
The most common phospholipids are:
phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylinositol (PI)
All the lipid molecules are derived from ________ except for sphingomyelin, which is derived from _______.
glycerol
sphingosine
Cholesterol has a:
polar hydroxyl group, a rigid steroid ring group, and a hydrocarbon tail
Cholesterol is intercalated among ________
membrane phospholipids
The interaction of the steroid ring with the hydrophobic tail of other phospholipids tends to ______
immobilize the lipid and decrease fluidity.
Lipids are forced to be ______ by cholesterol. The thickness of a membrane depends on the _______
straightened
amount of cholesterol.
difference in intracellular membranes and plasma membranes
Intracellular membranes have less cholesterol than the plasma membranes and are thinner than the plasma membranes
The mole percentage of cholesterol roughly doubles from
the ER (7%) to the Golgi (13%) and again from the Golgi to the plasma membrane (26%).
The two leaflets of the plasma membrane bilayer are not equivalent in terms of the
distribution of specific phospholipids.
________ are more abundant on the internal surface, while _________ are more abundant on the external surface.
Negatively charged phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylinositol (PI)
PC, sphingomyelin, and glycolipids
________ is thought to be distributed equally in the two leaflets/monolayers.
Cholesterol
Cholesterol is extremely important for _____
membranes and its abundance is closely regulated in the body.
We get cholesterol from (1) _____ and (2)_____
Uptake depends on _______
(1) ingestion and uptake and
(2) synthesis by the liver.
Uptake
depends on the low density lipoprotein receptor (LDLR)
there is _____ feedback for cholesterol production
negative feedback
if you get enough in the diet, you decrease synthesis and vice versa
Cholesterol synthesis depends ______.
approximately 30 enzymes
cholesterol first enzymatic step and rate determining step:
HMGCoA reductase (3-hydroxy-3-methylglutaryl coenzyme A reductase);
What blocks HMGCoA reductase?
statins, used to lower cholesterol, block this step.
statins block
the first enzymatic step and rate determining step in cholesterol production
HMGCoA reductase
Both cholesterol uptake and synthesis are regulated by the ________.
sterol regulatory element binding protein (SREBP), a protein containing a transcription factor that regulates both LDLR and all 30 of the synthesis proteins
If cholesterol is low, the transcription factor is _______.
released, moves to the nucleus and activates all these genes
Since cholesterol is in membranes, where and how would you design a sensor to detect cholesterol and how would the sensor be linked to the transcription factor?
The sensor is in the ER membrane, where cholesterol is lowest in the cell and changes would be easiest to detect
The cholesterol transcription factor is a _______
basic helix loop helix (bHLH) DNA- binding protein and is held inactive because it is part of a larger transmembrane protein (SREBP).
The cholesterol transcription factor only becomes active when _______.
it is cleaved from SREBP and then translocates to the nucleus
Where are the proteases that cleave SREBP to release the bHLH?
These proteases (there are two of them) are located in the Golgi complex. SREBP must be held in the ER until cholesterol is low and then SREBP must move to the Golgi where it gets cleaved and the bHLH released.
SREBP must be held in the ER until _____
cholesterol is low and then SREBP must move to the Golgi where it gets cleaved and the bHLH released.
three proteins are in a complex (SREBP, SCAP, and Insig), and when cholesterol is low, ________.
SREBP needs to move to the Golgi, where it is cleaved to release the transcription factor
SCAP:
SREBP cleavage activating protein
SCAP binds
binds both SREBP and sterols like cholesterol
Insig
binds SCAP when cholesterol is high
Insig binds SCAP only when ______ and when Insig binds, it ______.
This SCAP signal domain is recognized by a ______.
cholesterol is high
blocks a signaling part of SCAP
coat protein (COPII – more about this in a later lecture) for vesicles that move from the ER to the Golgi
Thus, as cholesterol concentration drops, Insig no longer binds SCAP and the SCAP/SREBP complex gets ________.
packaged into vesicles to go to the Golgi
One cleavage that releases bHLH cuts ________.
SREBP in the transmembrane domain
The cleavage of SREBP by bHLH (within the membrane) is called _____ .
RIP, regulated intramembrane proteolysis
RIP is critical for ________
Notch signaling in development and for cleavage of the amyloid precursor protein (APP) to produce the beta amyloid peptide in Alzheimer’s disease.
cleavage of the amyloid precursor protein (APP) to produce the beta amyloid peptide in Alzheimer’s disease requires
RIP
- When cholesterol levels are low SCAP-SREBP complex _____
dissociates from Insig.
The bHLH transcription factor is released from SREBP by _______
two step proteolysis- RIP- Regulated Intramembrane Proteolysis
S1P is ______, S2P is within _____
luminal
within the membrane – cleavage by both is required for activation
Nuclear bHLH SREBP moves to the nucleus, binds to DNA promoters, and activates many genes to produce _______
more LDLR to bring cholesterol into the cell and to increase all the enzymes involved in cellular synthesis of cholesterol.
Elevated cholesterol levels in plasma are linked to ______.
heart attacks
When LDL cholesterol levels are less than 100 mg/dl (total plasma cholesterol of 170 mg/dl),_______.
heart attacks are rare
It is likely that the level of plasma cholesterol needed for normal physiology is much lower because _______.
animals and newborn humans have LDL cholesterol levels in the range of 25-50 mg/dl.
These cholesterol levels are more in the expected range for the LDL receptor, which would have an optimal uptake for a plasma level about 25 mg/dl.
Of the roughly 22,000 genes in the human genome, ______
encode membrane transport proteins and ion channels.
about one-tenth (2200)
membrane transport proteins and ion channels are crucial _______.
(1) for
getting nutrients into cells and organelles and (2) for signaling
the Na-K ATPase, uses about __% of our ATP energy production to maintain the low concentration of ___ and high concentration of __ in cells.
30%
Na+
K+
Membrane transport proteins and ion channels form ________
aqueous pores through the membrane that are selective and regulated.
In addition to transmembrane proteins, many proteins are _______.
membrane-associated
These can be attached to lipids or to the extracellular or intracellular domains of transmembrane proteins
Most transmembrane proteins are thought to extend across the bilayer as
(1) a single α helix,
(2) as multiple α helices,
(3) as a rolled-up β sheet (a β barrel).
(4) Some of these are anchored to the cytosolic surface by an amphipathic α helix that partitions into the cytosolic monolayer of the lipid bilayer through the hydrophobic face of the helix.
(5) Attached to the bilayer solely by a covalently attached lipid chain—either a fatty acid chain or a prenyl group—in the cytosolic monolayer or,
(6) via an oligosaccharide linker, to phosphatidylinositol in the noncytosolic monolayer. (
7, 8) Finally, many proteins are attached to the membrane only by non covalent interactions with other membrane proteins.
Some of these “single-pass” and “multipass” proteins have a ________
covalently attached fatty acid chain inserted in the cytosolic lipid monolayer,
A variety of proteins (e.g., several hydrolytic enzymes) are anchored to the membrane by ______
glycosylphosphatidylinositol (GPI linkage).
This complex anchor to the membrane is found only on the exoplasmic/extracellular face.
Some bacteria, e.g. ______, secrete toxins that are _______.
Staphylococcus aureus and Listeria monocytogenes,
soluble, bind to membranes and form pores to rupture membranes
Aeromonas hydrophilia, secretes _______
a toxin that binds specifically to the GPI linkage, then inserts into the membrane, forms a pore and kills the cell.
SCAP conformational change to cholesterol
- Cholesterol binds to a lumenal part of SCAP
- Binding to Insig occurs.
- The result of 1 and 2 is the conformation of the cytosolic loop changes so that SCAP no longer binds COPII and is not trafficked with SREBP to the Golgi.
Phospholipids (phosphoglycerides) are composed of
a glycerol molecule bound to two fatty acyl chains, a phosphate and a polar head group that can be ehtnanolamine, choline, serine or inositol.
Sphingolipids are comprised of a _____
ceramide linked to a head group.
Ceramide is made of ______
sphingosine linked to a fatty acyl chain via an amide linkage.
Cholesterol is made of a ______
nonpolar hydrocarbon tail bound to a steroid ring structure with a small polar head group (a hydroxyl).
The _______ is the only hydrophilic element in a cholesterol molecule.
polar head
List the different ways proteins associate with membranes.
- they can be an integral protein that passes through the membrane,
- a peripheral proteins that attaches to one surface of the membrane
- a linked protein that it attached to the membrane via a sugar chain.
the horizontal composition of membranes is _____
asymmetric.
Membrane curvature is dependent on the _______
size of the head group versus the fatty acid tail.
Describe the concept of membrane fluidity.
Lipids can
- diffuse horizontally around the membrane.
- rotate and their tails can flex, altering the fluidity of a membrane.
- The more the individual lipids of the membrane move, the more fluid the membrane becomes.
- inserting cholesterols in the membrane stiffens the membrane
- the number of saturated (no double bonds) versus unsaturated (one or more double bond in the fatty acid tail) fatty acids contributes to membrane fluidity
Increasing double bonds increases
fluidity by creating kinks in the fatty acid tail that prevents the lipids from associating very closely.
cells have the ability to introduce ________
introduce double bonds into the fatty acid tails of their membranes.
There are two major ways to regulate cholesterol in the cell:
- by increasing uptake through the LDL receptor
- by de novo cholesterol synthesis through HMGcoA reductase.
Both of these pathways are sensitive to the amount of cholesterol present through an upstream regulatory sequence on the sterol response element gene (SRE).
Cholesterol regulates the HLH transcription factor responsible for binding the SRE.
SREBP stands for
Sterol response element binding protein
SREBP exists in the membrane of the
membrane of the endoplasmic reticulum
SREBP has a domain that faces _____ and is comprised of ________.
the cytosol
the HLH DNA binding protein that acts as a transcription factor
SCREBP has a tail that ________
extends into the ER with a cleavage site and another transmembrane domain extending into a cytosolic domain.
SCAP stands for:
SREBP activating protein
SCAP is a
cholesterol sensor
SCAB has _____ transmembrane domains as well as ____ cytosolic domains.
seven
two
Insig, is a _____that can bind ____.
transmembrane protein
SCAP
SCAP binds the _______.
the cytosolic domain of SREBP and Insig
Insig binds the part of SCAP that has a ________.
targeting sequence for movement to the golgi but only in the presence of cholesterol
Insig can only bind to SCAP when ______
cholesterol levels are high
