Membrane Proteins & Carbohydrates Flashcards
Why are membrane proteins needed?
They are required for the movement of metabolites across the membrane and cell signalling
Why is the membrane described as being “liquid crystal”?
It has a liquid character but remains ordered
It can freeze and become gel-like
How is it ensured that the membrane remains in the fluid region?
The fatty acids and cholesterol are present in different ratios to ensure that the membrane remains in the fluid region
What is meant by the phospholipid bilayer being a solvent for integral membrane proteins?
Membrane proteins freely diffuse laterally unless they are restricted
They CANNOT flip across the bilayer
How can different types of molecules diffuse across the phospholipid bilayer?
Polar, water-soluble molecules cannot pass through hydrophobic fatty acid tails
Ions and polar molecules can pass through the membrane via membrane protein channels
Hydrophobic molecules can diffuse through the membrane
What is the distribution of lipids across the membrane like?
The plasma membrane is not homogenous in its distribution of different lipids
What lipids are present in lipid rafts?
What are lipid rafts?
Lipid rafts are formed by lipids (and proteins) clustering into regions or domains
Lipid rafts contain sphingomyelin, cholesterol and glycolipids
Are membrane proteins found within lipid rafts?
Some membrane proteins prefer to cluster inside the domains
Some prefer to cluster away from lipid domains
What are the 3 types of membrane protein?
- integral (intrinsic) membrane proteins
- lipid-linked membrane proteins
- peripheral (extrinsic) membrane proteins
How do integral (intrinsic) membrane proteins span the membrane?
They span the membrane with single or multiple transmembrane (TM) segments
They have one or more segments embedded in the bilayer
What are the transmembrane regions of integral proteins made of?
Predominantly amino acids with hydrophobic side chains
They interact with fatty acid chains within the hydrophobic region of the bilayer
How can integral proteins be extracted from the membrane?
What is the effect of this on the cell?
They can only be extracted with organic solvents and detergents
This will damage and disrupt the membrane
What type of molecules are integral proteins?
They may be channels, transporters or receptors involved in cell adhesion
How does glycophorin A cross the membrane?
It has a single transmembrane domain
It is a single-pass protein that only crosses the bilayer once
What are the 3 domains of glycophorin A?
- hydrophilic domain on the extracellular side of the plasma membrane
- short transmembrane domain
- hydrophilic domain within the cytosol
What is the structure of the transmembrane domain of glycophorin A?
It is predominantly hydrophobic amino acids and it forms an alpha helix
What is meant by glycophorin A being asymmetrically orientated?
It is always found the same way up
This is because the extracellular domain is glycosylated
What is the function of glycophorins A and B?
They are major sialoglycoproteins found within the erythrocyte plasma membrane
They bear the antigenic determinants for the MN and Ss blood groups
What is significant about glycophorins being rich in sialic acid?
This gives the red blood cells a hydrophilic-charged coat
This enables them to circulate without adhering to other cells or vessel walls
How many times does bacteriorhodopsin cross the membrane?
It has multiple membrane domains
It is a multi-pass protein as it passes through the phospholipid bilayer more than once
It has 7 transmembrane helices
What is the structure of bacteriorhodopsin?
The 7 transmembrane helices are embedded in the hydrophobic interior of the bilayer
The TM domains are tightly packed into a bundle with short loops either side of the membrane
What is the function of bacteriorhodopsin?
It is used by archaea and is a proton pump
It captures light energy and uses it to move protons across the membrane out of the cell
What is meant by an alpha-helix protein?
When an integral protein crosses the lipid bilayer, it adopts an alpha-helical configuration
What are the only class of proteins that can perform functions both inside and outside of the cell and why?
Integral proteins
They are transmembrane so have regions inside and outside of the cell
What are acylated or lipid-modified proteins?
They are stably attached to the membrane through direct covalent interactions with lipids
These are lipid-linked proteins
What is the usual anchor that is found on a lipid-linked protein?
Glycosyl-phosphatidylinositol (GPI) anchor
GPI is attached to the C-terminus of a protein during post-translational modification and will anchor the protein to the membrane
What are examples of proteins which have a GPI anchor?
Prion proteins
Various viral proteins
Cellular proteins that contain myristic acid
How do the lipid-linked proteins attach into the membrane?
The proteins are covalently attached to a lipid
The lipid is inserted into the membrane
The protein does not interact with the hydrophobic region
What are the 3 main types of lipid-anchored proteins?
- fatty acylated proteins
- glycosylphosphatidylinositol-linked proteins (GPI)
- prenylated proteins
What is the difference in how GPI linkages and prenylation/fatty acylation attach proteins to the membrane?
GPI linkages anchor proteins to the extracellular surface of the plasma membrane
Prenylation and fatty acylation localises the proteins to the cytosolic surface of the plasma membrane
Where will myristoylated proteins be anchored?
To the membranes of the endoplasmic reticulum or the nucleus
How do peripheral (extrinsic) membrane proteins interact with the hydrophobic core of the bilayer?
They do not directly interact with the hydrophobic core
They interact with the lipid headgroups or other membrane proteins via ionic interactions
What will disrupt the ionic interactions between peripheral proteins and lipid headgroups?
A high salt (NaCl) solution
This will wash the peripheral membrane proteins off the bilayer in soluble form
What are examples of peripheral proteins?
spectrin and actin
regulatory protein subunits of many ion channels and transmembrane receptors
How can peripheral proteins be removed from the membrane?
They are easy to remove from the bilayer without damaging the membrane
They are soluble in aqueous solution
What is meant by cytoskeletal proteins?
They are peripheral membrane proteins that form a scaffold on the cytosolic side of the plasma membrane
This scaffold is attached to the cytosolic domains of the integral membrane proteins
What are the cytoskeletal proteins and their functions?
- spectrins - form 200nm long filaments
- ankyrin - bridges spectrin and band 3 proteins
- actin - joins spectrin filaments
- band 4.1 - this stabilises the spectrin-actin interaction
What is the role of the cytoskeleton?
It gives a cell its shape, offers support and facilitates movement through the microfilaments, microtubules and intermediate filaments
What happens if the peripheral proteins are removed from an erythrocyte?
- the erythrocytes “ghost” and lose their rigid shape
2. the membrane proteins become laterally mobile
What is the role of the red blood cell cytoskeleton?
It maintains the shape and rigidity of cells
It restricts the lateral movement of integral membrane proteins
What happens if there are mutations in the genes encoding spectrin and ankyrin?
Abnormally shaped erythrocytes
What results from the abnormally shaped erythrocytes produced due to mutations in spectrin and ankyrin?
Hereditary spherocytosis and elliptocytosis
They are degraded more rapidly by the spleen, resulting in anaemia
What is involved in spherocytosis?
The presence of spherocytes in the blood
These are sphere-shaped RBCs found in all haemolytic anaemias
What is involved in elliptocytosis?
An abnormally large number of a patient’s erythrocytes are elliptical
What is meant by dementia?
It is an umbrella term for describing a serious deterioration in mental functions
e.g. memory, language, orientation and judgement
What causes dementia?
Nerve cells in the brain die
This causes the connections between the cells to degenerate
What are the first signs of dementia often caused by?
Damage to the nerve cells in the hippocampus
This is the part of the brain that deals with memory
What are the “4 A’s” that describe clinical features of Alzheimer’s disease?
- amnesia (forgetting things)
- aphasia (language problems)
- agnosia (difficulty recognising and naming objects)
- apraxia (difficulties in complex tasks)
What are the other clinical features of Alzheimers?
- visuospatial difficulties
- functional impairment
- mood disorders
- personality change
- psychosis
What happens to the brain in Alzheimer’s disease?
The brain atrophies (shrinks) as nerve cells die
What causes neurone malfunction in Alzheimer’s disease?
An electrical signal is sent down the first neurone
It cannot be passed across the synapse
This leads to death of the second neurone
What are the 2 categories of drugs prescribed to Alzheimer’s patients?
How can they work?
- cholinesterase inhibitors
- NMDA receptor antagonists
They cannot cure Alzheimer’s, they can only treat the symptoms
What is the role of cholinesterase inhibitors?
They decrease the breakdown of acetylcholine
This means more ACh is available for communication between brain cells
What are examples of cholinesterase inhibitors?
Donepezil, rivastigmine, galantamine
How do NMDA receptor antagonists work?
They inhibit N-methyl-D-aspartate receptor when it is too active
They regulate the activity of glutamate, which is involved in brain functions such as learning and memory
What is the role of the NMDA receptor?
It allows for electrical signals between neurones in the brain and spinal column
What fills the brain of an Alzheimer’s patient?
Senile plaques
These consist mainly of the short amyloid-beta (A-beta) peptide
What is the A-beta protein derived from?
The larger membrane-bound amyloid precursor protein
Why can Alzheimer’s be described as a protein misfolding disease?
Due to the accumulation of abnormally folded amyloid beta protein in the brain
What are the properties of amyloid beta monomers?
- soluble
- contain short regions of beta sheet
- mainly alpha helical in membranes
What happens to amyloid beta monomers at sufficiently high concentration?
They undergo conformational changes to form a beta-sheet rich tertiary structure
This aggregates to form amyloid fibrils
What happens to the amyloid fibrils?
They deposit outside neurones to form plaques
What type of protein is more prevalent in Alzheimer’s patients?
What is its role?
Apolipoprotein E4
This is involved in cholesterol transport
How do statins affect Alzheimer’s disease?
They lower A-beta production in cells
They DO NOT slow the progression of Alzheimer’s
How do statins affect the membrane and why?
They alter cholesterol content, which alters the fluidity of lipid rafts in the membrane
What happens to amyloid precursor proteins in lipid rafts?
It is proteolytically processed in cholesterol-rich lipid rafts
This produces the amyloid-beta peptide
What enzyme is needed to cleave APP within the lipid raft?
How does this differ to outside of the raft?
Cleavage with B-secretase within the raft produces AB peptide
Outside the raft, APP is cleaved by a-secretase
What are oligosaccharides?
Carbohydrates whose molecules are composed of a relatively small number of monosaccharide units
They are found attached to proteins and lipids in the membrane
What is the role of oligosaccharides?
Cell recognition and cell binding
In proteins, where can a sugar be attached to form a glycoprotein?
What sugars are these?
Sugars can be attached to the hydroxyl group in the side chain of serine or threonine residues
These are O-linked sugars
Under what conditions can sugars be attached to the side chains of asparagine residues?
What does this form?
When the asparagine is in the consensus sequence (Asn-X-Ser/Thr)
As long as X is not proline
These are N-linked sugars
What is the difference between O-linked and N-linked sugars?
O-linked sugars are short and consist of 2-5 sugars
N-linked sugars are larger, branched structures that consist of 30-40 sugars
What is the main role of carbohydrates present on lipids and proteins in the membrane?
They help to stabilise them and prevent cleavage by extracellular proteases
They are involved in intracellular recognition
In the ABO blood group antigens, how do the antigens for each blood type vary?
O antigen has no extra sugar molecule
A antigen has an added N-acetyl-galactosamine residue
B antigen has an added galactose residue
