SFP14: Membranes And Membrane Proteins Flashcards
What are two pharmaceutical importances of membrane proteins?
Beta adrenergic receptor
Cystic fibroses transmembrane conductance regulator
What do beta adrenergic receptors regulate?
Smooth muscle relaxation
Agonists (of Beta2AR) are used in treating asthma
What is the importance of CFTR (Cystic fibrosis transmembrane conductance regulator)?
It plays a key role in maintaining nice fluid mucus secretions in lung and intestine
It is the most common genetic disease in the western world
What is the most common mutation for cystic fibrosis?
Loss of amino acid
What happens to the protein in the majority of people with CF?
They make the protein but it doesn’t get to the plasma membrane
What functions do membrane proteins have?
- receptors
- transporters
- channels
- structural
- enzymes
- markers
What is the definition of a membrane protein as a receptor?
A protein that receives a ‘signal’ (usually a chemical) and sets in place events that end up with a response to that signal
What is the example of rhodopsin?
It is the key protein involved in visual perception (light signal not chemical), upon light hitting it you get a change in chemical conformation of a bound chromophore, which signals a whole load of events which finishes with an electrical signal being transmitted down your optic nerve
Definition of membrane protein as a transporter
A protein that regulates the flux/flow/import/export/transport of chemicals from one side of a biological membrane to the other
What is the example of GLUT-4 as a transporter?
collects glucose from outside the cell when its in high concentrators and brings it inside the cell
Definition of membrane proteins as ion channels
A protein which opens up a continuous pore through the membrane through which ions flow according to their concentration gradient
Why are transporters and channels different?
A channel can be open all the way through unlike a transporter
What is quicker, a transporter or a channel?
Channels are far quicker than transporters as they are purely limited by diffusion rate
What is an example of membrane proteins as markers?
The example of MHC with infection
What are the three different categories of membrane proteins?
Integral membrane-spanning
Peripheral membrane-attached
Anchored
What parts of the peripheral protein are hydrophilic/phobic?
Peripheral proteins have a hydrophilic surface and a hydrophobic core
Removed from membrane by high salt buffers
once removed they are generally soluble in aqueous solution
What sort of protein might have a hydrophilic core and still sit in a membrane?
Channels generally form structures with a hydrophobic outside and hydrophilic inside
Porins… what is the size controlled by?
Number of strands (think of a barrel, planks of wood round the barrel)
Are strands around porins usually an even or odd number?
Even number (at least 9, as many as 22)
Why do porins tend to have even numbers of strands?
In a barrel, you have strands going up and down alternately round the barrel. When you get all the way round the first and last will be next to each other…
First amino acid in a polypeptide has its NH3+ and the last has its COO- group.
In porins those two groups are close enough to be covalently linked making the protein really stable in the HARSH environment that most bacteria inhabit.
Are membrane spanning regions predictable for alpha helices and beta sheets?
Alpha helices - yes
Beta sheets - no
What is the concept of a hydrophobicity scale?
Each amino acid has a given likelihood of being in a membrane spanning region of a protein
How does a hydrophobicity profile work?
- move a 7-11 amino acid ‘window’ along a protein’s primary sequence (7 amino acids is two alpha-helical turns, 11 is three)
- calculate mean hydrophobicity at each position
- plot mean hydrophobicity as a function of amino acid position in the primary sequence
- look for peaks of ca. 20-25 amino acids
What would be the prediction if a protein had 7 big hydrophobic areas?
It has 7 transmembrane regions
