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What are the key learning objectives for studying membrane structure?
1) Describe the molecular composition of biological membranes.
2) Describe the functional biophysical properties of biological membranes.
3) Describe classes of ion channels, their molecular structure, and their biophysical properties.
What are two functions of the membrane bilayer?
1) create and separate different environments
2) control and separate electrical charges
What does the cell membrane consist of?
The cell membrane consists mainly of a lipid bilayer with embedded membrane proteins
Name some of the lipids found inside the bilayer
-Nonpolar fatty acyl chains
-phospholipid polar heads facing to the outside
Name some of the lipids found on the outside of lipid bilayer
Glycolipids and the polar heads of the phospholipid
Name some of the proteins found on the lipid bilayer
- Integral proteins (single & multiple transmembrane helices which are found inside the membrane)
- Peripheral proteins covalently linked to a lipid
- Oligosaccharide chains of glycoproteins
What is the Physiological function of the membrane lipid bilayer?
It is to act as a permeability barrier that separates the intracellular and extracellular environments and prevents diffusive loss of important intracellular components
What are the 3 main components Lipids of cell membranes contain?
1) The hydrocarbon tail which contains mostly fatty acids
2) A glycerolphosphate molecule
3) A hydrophilic head group
-most of these head groups confer either hydrophobicity or hydrophlicity
What do membrane lipids contain?
-Membrane lipids contain two hydrocarbon tails, and have a high tendency to form planar bilayers.
-Individual units are cylindrical (cross-section of head equals that of side chain)
How do membranes form?
there is a spontaneous formation of lipid bilayer in water with the different hydrophobic and hydrophilic components
What do fatty acids form in the presence of water?
Fatty acids do not form bilayers, but micelles in aqueous solution.
-Individual units are wedge-shaped (cross-section of head greater than that of side chain)
How should one think about membrane lipids?
Membranes are highly dynamic and can be regarded as a 2-dimensional fluid.
Give some characteristics of fatty acids used in membranes
Fatty acids used in membrane lipids have lengths of the hydrocarbon tail of 12-24 carbon atoms. The fatty acids can be either saturated or contain double bonds.
Give an example of a saturated fatty acid
Stearic acid - all single bonded carbons in a chain
Give an example of an unsaturated fatty acid
Linoleic acid - mostly single bonded carbons but these chains have a big kink because there are double bonded carbons too
How can the head groups of lipids be formed?
The head groups of lipids can be formed by alcohols, amino acids or sugars. Phospholipids are either neutral or negatively charged.
Why does the lipid composition of membrane preparations contain multiple types of lipids?
the plasma membrane has sphingolipids, sterols, and other lipids that help to confer an organizing function in the membrane
What role does Cholesterol play in the membrane?
Cholesterol is a major constituent of many cellular membranes and reduces the fluidity of the membrane because of its rigid ring structure
What is a lipid raft?
Lipid (membrane) raft microdomains are enriched in cholesterol and sphingolipids and are involved with receptor signaling and intracellular trafficking of proteins and lipids
Describe the structure of a lipid raft
Proteins are not randomly put on membranes, they are actually often clustered into lipid rafts. They are rich in cholesterol and sphingolipids which helps to solidify membrane domains.
What are the 3 basic functions of membrane proteins?
Membrane proteins are embedded in the lipid bilayer and carry out specific functions important for
1) cell metabolism
3) cell-cell signaling
What type of human membrane has the highest ratio of protein to lipids?
Mitochondrial inner membrane (76:24) --> Electron Transport Chain and oxidative phosphorylation
What type of bacteria has a high protein to lipid ratio in its membrane?
Halobacterium purple membrane
Describe the ratio of a typical human membrane ratio of protein to lipid
It is about even --> Human erthrocyte is 49:43:8 for Protein:Lipid:Carb
Describe membrane proteins
-Like lipids, membrane proteins are amphipathic.
-Hydrophobic amino acids are localized within the membrane
-Charged an polar amino acids are exposed to water on the outside
Give the 5 Classes of integral membrane proteins
1) Receptors which transduce information from the extracellular to the intracellular side
2) Adhesion molecules, forming links between membranes and the extracellular matrix or neighboring cells
3) Pores and channels which mediate passive movement of ions and solutes across cell membranes
4) Pumps and transporters which actively move ions and solutes across membranes
What is the main question to ask when identifying the type of integral membrane protein?
ask yourself, do we need energy to pump the ions or particles across?
Give 7 examples of pores and channels which mediate passive movement of ions and solutes across cell membranes
1) Inward rectifier K+ ion channel
2) Calcium-activated ion channel
3) Voltage-dependent K+ channel
4) Voltage-dependent Na+ channel
5) Nicotinic Acetoylcholine Receptor cation channel
6) Ionotrophic Glutamate Receptor cation channel
7) CFTR chloride channel
Describe the opening and closing of ion channels
Ion Channels can be non-gated (always open) or gated (open only at certain times). They open and close in conjunction to a chemical stimulus.
What are the 3 types of ion channels?
1) Mechano-sensitive channels
2) Voltage-sensitive channels
3) Chemo-sensitive channels
What is the structure of the inward rectifier K+ ion channel?
There are 4 subunits and the monomer of the inward rectifier potassium channel spans the membrane two times.
What is the molecular architecture of potassium channels?
The channel is assembled from four identical subunits. They are crystal structures with pore channels. Na often prefers to remain in the cavity. The channel has a shape of an inverted teepee and contains glysine, tryosine, and glysine repeating patterns
Describe the mechanism of action for Calcium-activated ion channels?
This is a potassium channel gated by Ca+
1) Ca+ travels up into the TMD from the Ca binding cytoplasmic domain in order to open the channel
2) the Ca+ binding site is found below the transmembrane domain
3) at a high intracellular concentration of Ca+ it will open
4) at a low intracellular concentration of Ca+ it will close
What is the topology of the tetrameric voltage-dependent K+ channel?
- Voltage sensing domain
- Pore forming domain
- Selectivity filter
- Voltage sensor
- Pore loop
Describe the mechanism of action for opening voltage-activated ion channels
The movement of the positively-charged S4 opens and closes voltage-activated ion channels. The active state has a positive charge on the intracellular side and opens the channel via S4 domain.
What would close a voltage-gated channel?
A negative charge on the inside of a cell attracts the positively-charged S4 domain down and this action will close the channel
Describe Voltage-dependent Na+ channels
Voltage-dependent Na channels have four non-identical subunits linked to each other. The Na+ channel is by and large a polypeptide chain. the S5 and S6 domains form the core part of it.
What is a Nicotinic acetylcholine receptor?
Nicotinic acetylcholine receptor is a chemo-sensitive cation channel. It is a ligand-gated channel that is found in muscles. It facilitates the first rxn in muscle contraction
What does a Nicotinic acetylcholine receptor do?
1) transports Na+ and Ca+ from the outside of the cell to the inside
2) transports K+ from the inside to the outside of the cell
Describe the structure of the nicotinic acetylcholine receptor
-it has 5 subunits with 4 TMDs
-the M2 membrane spanning domains face the pore of the channel
-the pore of the channel (both sides exposed) are negatively charged to attract cations
Describe how the structure of the nicotinic acetylcholine receptor confers its function
-The channel is blocked when it is pinched together in a kink!
-There are a series of hydrophilic molecules which make it more favorable for the conduction of the cations
What results in the opening of the channel in nicotinic acetylcholine receptors?
Acetylcholine binding to the acetylcholine receptor induces structural changes that result in opening of the channel.
**There is also the closed densensitized state which allows the muscle to relax.
What are the most common chemosensitive channels in the central nervous system?
Ionotropic Glutamate Receptors
They are selective for cations (Na+, K+ & Ca2+)
Describe the CFTR chloride channel
The cystic fibrosis transmembrane regulator (CFTR) is a chloride channel. Mutations to this channel lead to cystic fibrosis.
-uses passive transport
-the ligand it uses is ATP but the energy resulting in cleavage is not directly involved in the transport of Cl-
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