Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Personal ESA 2 Membranes and Receptors > Session 1 > Flashcards

Session 1 Flashcards

1
Q

What are the functions of a biological mebrane?

A
  • Continuous, highly selective permeablity barrier
  • Control of the enclosed chemical environment
  • Recognition - signalling moecules, adhesion protein and immune surveillance (e.g. presenting ‘self’ antigen so cells are not attacked by own immune system)
  • Signal generation in response to stimuli (involving interactions with other cells) which can be electrical or chemical.
  • Communication - control the flow of information between cells and theirenvironment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Are all membranes the same?

A

No

Different membanes have specialised functions e.g. mitochondrial membrane is specialised for ATP generaton by oxidaive phosphorylation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What kind of functions can different regions of a biological membrane have?

A

Interaction with basement membrane

Interaction with adjacent cells

Absorption of body fluids

Secretion

Tranport

Synapses (nerve junctions allow communication between cells)

Electrical signal conduction

Changing shape may change the properties of a particular region.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the General Membrane Composition?

A

Varies with source of membrane (depends on function and location point on cell) but generally membranes contain approximately (dry weight):

40% Lipid

60% Protein

1-10% Carbohydrate

sea of lipids packed with proteins

NB: membranes are hydrated structures so 20% of total weight is WATER

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the major property of membrane lipids?

A

They are AMPHIPATHIC molecules (they contain both a hydrophilic and a hydrophobic moiety). Distribution varies depending on cell type.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Name the predominant membrane lipid. Give an example

A

Phospholipid: 3C (Glycerol) backbones with two fatty acid chains and a phosphate head group.

E.g. Phosphatidylcholine (choline head group attached to the phosphate group which is attached to the glycerol)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Give examples of phospholipid head groups

A

Choline

Serine

Ethanoloamine

Inositol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the structure and properties of a phospholipid

A
  • Wide range of head groups (choline, amines, amino acids, sugars) which are POLAR and HYDROPHILIC.
  • Fatty acid chains (length between C14 and C24 but C16 and C18 most prevalent) resulting in all fatty acids being approximately the same length so membrane is approximately the same width.
  • In unsaturated fatty acids, the cis double bond introduces a kink which REDUCES phospholipid packing.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is Sphingomyelin?

A
  • Plasmalogen (non-classical phospholipid)
  • Only phospholipid not based on glycerol
  • In the membrane, the conformation of Sphingomyelin resembles other phospholipids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the structure of Glycolipids

A
  • Replacing the phosphocholine moiety with a sugar makes a Glycolipid
  • Sugar containing lipids (no phosphate head groups)
  • Cerebrosides: head group conains a single sugar monomer
  • Gangliosides: head group contains oligosaccharides (sugar multimers)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What structure do amphipatic molecules form in water and which structure is favoured for phospholipids and glycolipids?

A
  • Form one of two structures in the water, Micelles and Bilayers
  • Bilayers are the favoured structures for Phospholipids and Glycolipids
  • Bilayer formation is spontaneous in water, driven by Van der Waals attractive forces between hydrophobic tails.
  • The co-operative structure is stabilised by non-covalent forces: electrostatic and hydrogen bonding between hydrophilic moeties and interactions between hydrophilic groups and water.
  • Pure lipid bilayers have a very low permeability to ions and most polar molecules.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Is the Phospholipid Bilayer dynamic?

A

Yes, highly so (moving around all the time)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the influence of cis double bonds in bilayer structure

A

The kinks (caused by double bonds) in unsaturated fatty acid chains aid membrane dynamics by reducing phospholipid packing - they disrupt the hexagonal packing of phospholipids and so increase mmbrane fluidity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What modes of mobility do lipid moecules possess in a lipid bilayer?

A

Membrnes are fluid structures

  • Intra-chain motion (kink formation in the fatty acid chains - FLEXION)
  • Fast axial rotation
  • Fast lateral diffusion within the PLANE of the bilayer
  • Flip-Flop: movement of lipid molecules from one half of the bilayer to the other on a one for one exchange basis.
  • NOTE: Flip-flop is very rare
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the structure and property of cholesterol

A

Hydrophobic

Rigid Ring Structure

It is a plasma membrane lipid - 45% of total membrane lipid.

Distribution of different lipids is tissue specific and related to function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What effect does cholesterol have on the membrane bilayer?

A
  • Maintains constant environment and integrity of lipid bilayer by maintaining fluidity.
  • Stabilises the plasma membrane by hydrogen bonding to the fatty acid chains.
  • THIS ABOLISHES THE ENDOTHERMIC PHASE TRANSITION OF PHOSPHOLIPID BILAER
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What effect does cholesterol have at HIGH temperatures?

A

Cholesterol decreases vibration (reduces phopholipid chain motion) which can cause fractures in the membane or increasing protein conformation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What effect does cholesterol have on LOW temperatures?

A

Phospholipids can aggregate at low temperatures (crystallisation) which can cause fractures so cholesterol reduces phospholipid packing, increasing membrane fluidity and therefore crystallisation.

Paradoxical effects: cholesterol reduces phospholipid packing, increasing membrane fluidity (at low temps) but at high temps, it reduces phospholipid chain motion, decreasing membrane fluidity

19
Q

What is the functional evidence for proteins in membranes?

A

They carry out distinctive functions:

  • Enzymes
  • Transporters
  • Pumps
  • Ion channels
  • Receptors
  • Transducers

Functional Evidence:

  • Facilitatd Diffusion
  • Ion gradients
  • Specificity of Cell responses

Protein content can vary from ~18% in myelin to ~75% in mitochondria

20
Q

What is the Biochemical Evidence for Proteins in Membranes

A
  • Membrane fractionation + gel electrophoresis (SDS-Page)
  • Freeze Fracture
21
Q

What are the three modes of motion (of proteins) permitted?

A
  1. Conformational change (important for function)
  2. Lateral
  3. Rotaton

NO FLIP FLOP BECAUSE THEY HAVE LARGE HYDROPHILIC MOIETIES AND LARGE AMOUNTS OF ENERGY WOULD BE REQUIRED TO PASS THROUGH THE HYDROPHOBIC REGION OF THE BILAYER

22
Q

What are the restraints on membrane protein mobility?

A

Proteins are fixed in position

  • Lipid mediated effects: proteins tend to separate out into the fluid phase or cholesterol poor regions
  • Membrane protein associations (a lot of signallig proteins aggreggate within cholesterol rich regions)
  • Association with extra-membranous proteins (periheral proteins) e.g. cytoskeleton
  • Aggregates tend to lead to more sluggish movement
  • Tethering e.g. to the basement membrane or cytoskeleton
  • Interaction with other cells will tether adhesion molecules between the two cells.
23
Q

Describe the structure of a lipid bilayer

A

Biological membranes are composed of a lipid bilayer with associated membrane proteins which may be deeply embedded in the bilayer (integral) or associated with the surface (peripheral)

24
Q

Describe a Peripheral Membrane Protein

A
  • Bound to surface
  • Electrostatic and hydrogen bond interactions
  • Removed by changes in pH or in ionic strength (can be ‘washed off’)
25
Q

Describe an Integral Mmbrane Protein

A
  • Interact extensively with hydrophobic domains of the lipid bilayer
  • Cannot be removed by manipulatin of pH and ionic strength
  • Are removed by agents that compete for non-polar interactions (therefore destroying the membrane) e.g. Detergents and organic solvents
26
Q

Why is membrane asymmetry important?

A
  • Asymmetrical orientation of proteins is important for function e.g. a receptor for a hydrophilic extracellular messenger molecule such as insulin must have its recognition site directed towards the extracellular space to be able to function.
27
Q

Why is the plasma membrane described to be fluid?

A
  • Contains hydrophobic integral component such as lipids and membrane proteins that move laterally through the membrane so the membrane is not solid - more fluid.
  • The membrane is depicted as mosaic because it is made up of many different parts such as integral proteins, peripheral proteins, glycoproteins, phospholipids, cholesterol etc.
28
Q

Describe Secretory Protein Synthesis / Protein Secretion Pathway

A
  1. Free ribosome initiates protein synthesis from mRNA molecule
  2. Hydrophobic N-terminal signal sequence is produced.
  3. Signal sequence of newly formed protein is recognised and bound to by the Signal Recognition Particle (SRP)
  4. Protein synthesis stops.
  5. GTP-bound SRP directs the ribosome synthesising the secretory protein to SRP receptors on the cytosolic face of the ER.
  6. SRP dissociates
  7. Protein synthesis continues and the newly formed polypeptide is fed into the ER via a pore in the membrane (peptide translocation complex)
  8. Signal sequence is removed by a signal peptidase once the entire protein has been synthesised.
  9. The ribosom dissociates and is recycled
29
Q

What is a Hydropaty Plot?

A

Some membrane proteins have multiple (hydrophobic) transmembrane domains. Hydropathy plots can detect the number of hydrophobic transmembrane domains a protein has.

R groups of amino acid residues in transmembrane domains are largely hydrophobic. Transmembrane domains are often alpha-helical.

Glycophorin is a single transmembrane domain protein. Bacteriorhodopsin is a multiple transmembrane domain protein. Hydrohobic domains are orange (~20 amino acis are needed to span the domain)

30
Q

How are all proteins of a particular type organised? Give an example

A

All proteins of a particular type are organised facing a particular way. For Glycophorin, the N-terminal is inside and the C-terminal is outside.

31
Q

How does Mmbrane Protein Synthesis Drect Protein Orientation

A
  • Memrane proteins need to span the membrane of a vesicle rather than be contained within it.
  • Before synthesis progresses very far, the translation of the proteins is halted until the ribosome has een transferred to the rough ER. The signal sequence (hydrophobic , 18-30 aa, flanked by basic residues at the N-terminus) is recognised by a large protein/RNA complex (SRP)
  • When the SRP binds, it prevents further protein synthess while the ribosome is in the cytoplasm. On the ER, the SRP is recognised by a receptor and interacts. SRP dissociates
  • the Signal sequence interacts with a Signal Sequence Receptor (SSR) within a protein translocator complex (Sec61) in the ER membrane which directs further synthesis through the ER membrane.
  • The ribosome becomes anchored to this pore complex through which the growing polypeptide chain is extruded. The passage of the membrae protein though the membrane must be arrested via a Stop Transfer signal (which the ribosome comes across in the membrane)
  • The stop transfer signal remains in the ER membrane and the rest of the protein is translated outside the ER in the cytoplasm. Therefore the protein spans the membrane.
32
Q

What is the Stop Transfer Signal?

A

Regin of highly hydrophobic primary sequence (~18-20 amino acids needed to span a phospholipid membrane followed directly by charged amino acids which in alpha-helical form is long eough to span the hydrophobic core of the bilayer).

This sequence forms the trans membranous region of the protein.

Transmembrane regions are largely mde up of hydrophobic, small or polar uncharged amino acids

33
Q

How is a membrane protein released from the protein translocator into the lipid bilayer?

A
  • A lateral gating mechanism releases the membrane protein from the protein translocator into the lipid bilayer
  • The ribosome then presumably detaches from the ER and protein biosynthesis continues in the cyoplasm. The result is a transmembrane protein with its N-terminal directed into the lumen and its C-terminal to the cytoplasm
  • For both secretory prtens and membrane incorporated protei, the signal sequence is cleaved from the new protein by signal peptidases even before protein synthesis is completed.
34
Q

But how are membrane proteins with a lumen-directed C-terminal orientated?

Many membrane proteins lack a cleavable N-terminal signal sequence but rather contain internal start-transfer signal’ sequences, raising the question of how their orientation is defined?

A
  • The positioning of positively charged (basicamino acids) at either the N- or C- terminal end of the start-transfer sequence defines their orienation which in turn specifies the orientation of the mature membrane protein.
  • Wher positively charged residues are located at the N-terminal end, the C-terminal section passes into the lumen
  • Where psitviely charged residues are located at the C-terminal end, the N-terminal section of the protein passes into the lumen
  • Binding of positive residues within signal and start-transfer sequences on the cytoplasmic side of the protein translocator complex provides an explanation that fits all scenarios
35
Q

When a protein has multiple transmembrane domains, what drives the insertion of other domains?

A
  • Likely that the folding of the protein againstthe constraint of the first transmemrane segment is the driving force for the insertion of the ther domains
  • Possible that a series of start and stop transfer sequences within the primary structure control membrane insertion
  • The association of lumenal binding proteins (e.g. BiP)related to the family of heat-shock (chaperone) proteins also assist in stabilizing the partially folded growing pepide.
36
Q

What are the restraints on protein MOVEMENT?

A

The lateral diffusion of proteins through the membrane is affected by:

  • Size
  • Protein aggregation (membrane protein associations) - Association with extramembranous intracellular (e.g. cytoskeleton) or extracellular proteins (e.g. basement membrane)
  • Lipid mediated effects: Proteins tend to separate out into the fluid phase or cholesterol poor regions.
37
Q

How can you prepare an erythrocyte ghost from an erythrocyte membrane? What does it reveal?

A
  • Erythrocyte ghosts can be prepared by osmotic haemolysis to release cytoplasmic components.
  • Analysis of ghost membranes by gel electrophoresis reveals over 10 major proteins. Most of these proteins are peripheral and are released when ghost membranes treated with low or high ionic strength or by changing the pH. The peripheral proteins must be located on the cytoplasmic face since they are susceptible to proteolysis only when the cytoplasmic face of the membrane is accessible.
  • Proteins bands 3 and 7 are integral. They contain covalently attached carbohydrate units and are thus glycoproteins. A great variety of carbohydrate structures is possible on different proteins. Specific carbohydrate groups on membrane proteins may be important for cellular recognition to allow tissues to form and in immune recognition.
  • After the peripheral proteins are removed by saltwashes, a membrane skeleton on the cytoplasmic face of the membrane is left. This is the erythrocyte skeleton.
38
Q

Describe the Structure of the erythrocyte skeleton

A
  • Network of spectrin and actin molecules
  • Spectrin is a long, floppy rod-like molecule. Alpha and beta subunits wind together to form an antiparallel heterodimer and two heterodimers then form a head-to-head association to form a hetero-tetramer of alpha2-beta2.
  • Thes rods are crosslinked into networs by short actin protofilaments (~14 actin monomers) and band4.1, and adducin molecules which form interactions towards the ends of the spectrin rods.
  • The spectrin-actin network is attached to the membrane through adapter proteins.
  • Ankyrin (band4.9) link spectrin and Band 3.
  • Band 4.1 link spectrin and Glycophorin A (Band 7) respectively.
  • attachment of integral membrane proteins to the cytoskeleton restricts the lateral mobility of the membrane protein
39
Q

What is the function of the erythrocyte skeleton?

A
  • holds the shape of RBCs
  • without the skeleton, RBCs round up, becoming more spherical and are lysed by shearing forces in capillary beds and cleared by the spleen.
  • gives the cell some plasticity as it allows the cell to change shape and pass through tight capillaries - very important in maintaining the deformability necessary for erthrocytes to make their passage through capillary beds without lysis.
40
Q

Describe Hereditary Elliptocytosis

A
  • A common defect resulting in Specrin molecles unable to form heterotetramers
  • This results in fragile elliptoid cells which lead to haemolytic anaemia
41
Q

Describe Hereditary Spherocytosis

A
  • In the common dominant form, Spectrin may be depleted by 40-50% (mutation results in less protein production leading to cytoskeleton being less intact)
  • Erythrocytes round up and become much less resistant to lysis during passage through the capillaries
  • cleared by spleen
  • The shortened in vivo survival of red blood cells and the inability of the bone marrow to compensate for their reduced life span lead to haemolytic anaemia.

*

42
Q

How can simple treatment with cytochalasin drugs alter the deformability of the erythrocyte?

A

The drugs cap the growing end of polymerising actin filaments which can alter the deformability of the erythrocytes.

43
Q

Describe Post-Translational Processing

A
  • The polypeptide chain is further processed as it passes from the ER and through the cis to trans Golgi.
  • The new protein continues along the secretory pathway until the secrtory vesicle fuses with the plasma membrane.
  • At this point secreted proteins are delivered such that the regions of the protein that were located in the cytoplasm during synthesis remain with this orientation

Personal ESA 2 Membranes and Receptors (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions