Cell membrane structure Flashcards
1
Q
What membranes do prokaryotes have?
A
Either one cell membrane (gram- positive bacteria) or have inner and outer membranes (gram- negative bacteria)
2
Q
What membrane do eukaryotic cells have?
A
Many membranes
3
Q
What are the 6 membrane functions?
A
- Provide a functional barrier- compartmentalisation of cells
- Provide cells with energy (from chemical and charge gradients)
- Organise and regulate enzyme activities
- Facilitate signal transduction
- Supply substrates for biosynthesis and for signalling molecules
- Protein recruitment platform
4
Q
What are the 3 lipids that membranes contain?
A
- Glycerophospholipids (phospholipids)
- Sphingolipids
- Sterols
5
Q
What are fatty acid chains?
A
-Fatty acid chains are long aliphatic carbon chains with a terminal carboxylic acid
- Fatty acids vary in length, double bond number and double bond position. Two fatty acid chains in a lipid can be different in length
6
Q
What are saturated lipid tails?
A
Fatty acids in lipid tails that do not have double bonds between adjacent carbon atoms. This lipid tail is relatively straight
7
Q
What are unsaturated lipid tails?
A
Fatty acids in lipid tails that contain one or more double bonds between adjacent carbon atoms. Unsaturated lipid tails can have a cis double bond- makes a 30 degree kink or a trans double bond that does not affect their structure
8
Q
What are Glycerophospholipids?
A
- chemical diversity arises from the combination of the two fatty acids, the linkage at the sn-1 position and the head group
- The sn-1 fatty acid is usually saturated (without double bonds) or monounsaturated
- The sn- 2 fatty acid is more often monounsaturated or polyunsaturated (multiple double bonds)
9
Q
What charge do anionic phospholipids have?
A
PS, PI, PG & CL
= net negative
10
Q
What charge do zwitterionic phospholipids have?
A
zero charge
11
Q
What do PS & PE contain?
A
reactive amines that can participate in H bonds
12
Q
What do PI, PC & CL contain?
A
- Relatively bulky- affects their packing
13
Q
What are Sphingolipids?
A
- Spingolipids are built on sphingoid base, N- acyl chain and head group
-N- acyl chain is attached via an amide linkage
14
Q
What is the most common sphingolipid?
A
- Most common sphingolipid is sphingomyelin (SM) that has a phosphcholine headgroup
15
Q
How do sphingolipids interact with cholesterol?
A
Amide groups form H bonds
16
Q
What is different about N- acyl chains of sphingolipids?
A
Tend to be more saturated and can be longer than the acyl chains of glycerophospholipids
17
Q
What are Glycosphingolipids?
A
- Complex glycosphingolipids have different oligosaccharides as head group. Their structures are composed of various building blocks (mainly sugars)
- Glycosphingolipids are found exclusive in the outer leaflet of the membrane
- Important role in interactions of the cell with its surroundings (Cell- cell adhesion)
- Allow membranes to act as recognition sites for certain chemicals
18
Q
What are sterols?
A
- Sterols have a hydroxyl group and a hydrocarbon tail
- Cholesterol is the most common sterol in animals. Ergosterol is found in yeast and fungi membrane.
- Size and shape allows cholesterol to interact with pockets in membrane proteins
19
Q
What is cholesterol?
A
most common sterol in animals
20
Q
What is ergosterol?
A
found in yeast and fungi
21
Q
What is sitosterol & stigmasterol?
A
found in plants
22
Q
What does sterols do?
A
increases thickness, packing and compressibility of membranes while it decreases mobility of lipids and proteins
23
Q
What are hydrophilic molecules?
A
dissolve in water
contain groups that can form electrostatic interactions or H bonds with water molecules
24
Q
What are hydrophobic molecules?
A
Insoluble in water
cannot form energetically favourable interactions with water
25
What do hydrophobic molecules do in water?
- force adjacent water molecules to reorganise
26
Why do lipids spontaneously aggregate?
to bury their hydrophobic tails in the interior and expose their hydrophilic heads to water
Depends on their shape lipids can form bilayers or micelles
27
What are the 3 types of membrane curvature?
- Cylindrical (flat membrane)
- Conical (negative curvature)
- Inverted- conical (positive curvature)
28
What is membrane curvature?
The relative size of the head group and hydrophobic tails of lipids affect the shape of the lipid and the spontaneous curvature of the membrane
29
What does negative spontaneous curvature of PE lead to?
- bilayer- disrupting properties, which might promote processes that involve the generation of non- bilayer membrane intermediates, such as fusion
30
What is membrane asymmetry?
- Lipid asymmetry is functionally important
- Glycolipids are oriented towards the exterior of the cell
- Second messengers in signalling pathways are oriented towards the interor of the cell
31
What happens to phosphatidylserine?
- Phosphatidylserine in animal cells translocate to the extracellular monolayer when such cells undergo cell death, or apoptosis. This acts as a signal to neighbouring cells, e.g. macrophages, to phagocytose the dead cell and digest it.
32
What are the 3 different movements of lipids in the bilayer?
- Rotational
- Lateral
- Transverse
33
What is rotational lipid movement?
The spinning of lipids around its axis. Does not alter its position but affects its interaction with neighbouring molecules
34
What is lateral lipid movement?
Neighbouring lipids exchange places. It allows lipids to change position within a bilayer leaflet
35
What is about transverse lipid movement?
The exchange of molecular between leaflets. Lipids can move across a bilayer membrane spontaneously by transverse diffusion or their translocation can be mediated by proteins (unidirectional or bidirectional)
36
What does protein mediated lipid translocation sometimes require?
the input energy (ATP hydrolysis)
37
What is spontaneous translocation?
bidirectional
no energy needed
non specific
38
What is P- type flippase translocation?
inward movement of lipids
ATP required
specific
39
What is ABC flippase translocation?
Outward movement of lipids
ATP required
Specific
40
What is scamblase translocation?
bidirectional
no energy needed
non- specific
Ca2+ dependent
41
What is the model of the membrane?
Fluid mosaic model= the bulk of the lipids form the bilayer providing the solvent for embedded proteins
- Bilayer= fluid, lateral mobility of lipids and some proteins, mosaic as proteins are scattered across it
42
What is the lateral organisation of membranes?
Concept of membrane domains or rafts
Model suggests that in a eukaryotic plasma membrane there will be a large number of domains
43
What are domains and rafts?
Enriched with cholesterol & sphingomyelin, rafts= proteins are either excluded or included
Lipid rafts are expected to be different in their lipid composition, lifetimes and sizes
44
3 types of membrane proteins
Integral (intrinsic) membrane protein
Lipid- linked membrane protein
Peripheral (Extrinsic) membrane proteins
45
5 different roles of integral membrane proteins
- Transport
- Enzymatic activity
- Signal transduction
- Cell- cell interactions
- Attachment to the cytoskeleton or the extracellular matrix
46
Integral MP= Transport
move molecules across cell membrane by changing shape
47
Integral MP= enzymatic activity
Enzymes carry out diverse catalytic functions. They participate in electron transport, and metabolism of phospholipids and sterols
48
Integral MP= signal transduction
Membrane proteins transfer information (signals) in response to the binding of a ligand or molecule
49
Integral MP= cell-cell interactions
Glycoproteins are recognised by proteins in another cell, promoting short- lived cell interactions
50
Integral MP- attachment to the cytoskeleton or the extracellular matrix
Integral membrane proteins= non- covalently bound to proteins in the cell's cytoskeleton.
Regulate the cell shape or stabilise proteins position in the membrane.
Integral membrane proteins also bind to extracellular matrix= allows for cell-cell adhesion
51
What is glycophorin A?
- first integral membrane protein to be sequenced
- The helix is formed by H bonds between the aminoacids in the transmembrane region
- Single polypeptide chain of 131 aa in 3 domains
52
What are the 3 domains of glycophorin A?
-Hydrophilic domain- glycosylated and residues on extracellular side of the erythrocyte plasma membrane
-Short predominantly hydrophobic transmembrane domain= forms alpha helix
- Hydrophilic domain= resides in the cytosol of the erythrocyte
53
What is Bacteriorhodopsin?
- First integral membrane protein whose structure was determined
- 7 transmembrane helices
- 20-30 amino acids in an a helix required to cross the 45A thick membrane
- Multiple transmembrane domains packed in bundle
- Short loops on either side of membrane
54
What is the glucose transporter? (GLUT)
- All cells, abundant in cells lining small intestine
- GLUTs membrane spanning region= 12 a- helices
55
What are the steps for glucose transport?
1- Glucose binds to binding site open to outside
2- Transport protein shifts to alternative conformation
3- Glucose is released to the inside and protein returns to its original conformation
56
What are ion channels?
- integral membrane proteins that modulate the flow of ions in and out of the cell
- Don't require large conformational change
- Channels are selective
- Open in response to ligand binding, electric potential, pH, temp & pressure from lipids
57
What are peripheral membrane proteins?
- Bind to the surface of the membrane
- Interact with lipid headgroups or with charged group on other proteins
- hydrophobic interaction with the lipid acyl chains also contribute to their association to membranes
58
How does binding of peripheral proteins occur
- Occurs via lipid binding module or via positively charged surfaces that recognise specific lipids in the membrane
59
How do lipid binding domains vary?
-Varying degree of anionic surfaces
-Each lipid binding domains has its one binding mechanism depending on its function
- Some lipid binding domains are highly specific and bind only to a very specific lipid
60
How are proteins linked to a lipid?
- Covalently
- Lipid is inserted in the membrane
- Different proteins use different lipids for attachment
61
Lipid- linked membrane proteins
Lipid modifications also stabilise the interactions of membrane proteins with membranes
Often proteins have more than one lipid chain as one chain is not sufficient for binding
62
Myristoyl groups
connected to glycine residues
63
Palmitoyl groups
covalently linked to cystine or serine residues
64
Mutations on the myristoyl & palmitoyl sides
- shown to result in the loss of binding of peripheral membrane proteins to membranes
65
Where are carbohydrates found in the membrane?
- Attached to lipids= glycolipids
- Attached to proteins= glycoproteins
Both are most of the time located on the extracellular face of membrane
66
What are O linked glycoproteins?
- Contain a carbohydrate attached to the oxgen atom in the side chain of serine or threonine
- Often short consisting of 2-5 sugars
67
What are N linked glycoproteins?
- Contain a carbohydrate attached to the amide nitrogen atom in the side chain of asparagine amino acid
- An asparagine residue can accept an oligosaccharide only if the residue is part of an Asn- X-ser or Asn- X- Thr sequence, in which X can be any residue
- Usually, large branched structures with as many as 30-40 sugar residues
68
Importance of carbohydrates
- Stabilisation of proteins
- Cell- cell recognition
69
Example of Importance of carbohydrates
- Blood group antigens (ABO) are sugars
- ABO blood group antigens are attached to lipids in the RBC membrane
- The antigens expressed on the RBC determine blood group
- No extra sugar in O antigen
- N- acetyl- galactosamine in A antigen
- Galactose in B antigen
70
What is alzheimer's disease?
Fatal neurodegenerative disease that is the most common cause of dementia
71
Dementia
- Umbrella term
- describes a serious deterioration in mental functions e.g.
- memory
- language
- orientation
- judgement
72
What is AD caused by?
nerve cells in the brain dying and the connections between the cells degenerating
Such that normal communication between and within the nerve cells is lost
73
AD- neurons malfunction
- In the brains of those suffering from Alzheimer's disease, the neurons malfunction and eventually die
- Results in both the chemical signalling between the nerve cells and the electrical signalling within them to go wrong
74
AD- mechanism
- Post mortem, the brain of an alzheimer's individual is found to be full of senile plaques which consist mainly of the short amyloid- beta peptide
- This peptide is derived from the larger membrane bound amyloid precursor proteins
75
AD- lipid rafts/ cholesterol
- The proteolytic processing of APP in the cholesterol- rich lipid rafts produces the toxic amyloid beta peptide
- Cleavage of APP in other regions of the membrane prohibits the formation of amyloid- beta
- Modulation of the structure of the membrane may influence the production of amyloid- beta and progression of AD
76
What is hereditary spherocytosis (HS)?
- Red cell membrane disorder
- Occurs in all racial groups
- Disease severity= highly variable
- 60% of the cases have a moderate manifestation of the disease
77
What happens is HS?
- Loss of conhesion between plasma membrane and the skeleton as a result of the defective anchoring of the skeletal network in the membrane
- Cell shape change to spherocytes
78
Most common cause of HS
leads to anemias
- deficiencies in ankyrin (60%)
spectrin (20%) Band 3 (15-20%)
