SFP14: Membranes And Membrane Proteins

Question 1

What are two pharmaceutical importances of membrane proteins?

Answer 1

Beta adrenergic receptor

Cystic fibroses transmembrane conductance regulator

Question 2

What do beta adrenergic receptors regulate?

Answer 2

Smooth muscle relaxation

Agonists (of Beta2AR) are used in treating asthma

Question 3

What is the importance of CFTR (Cystic fibrosis transmembrane conductance regulator)?

Answer 3

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

Question 4

What is the most common mutation for cystic fibrosis?

Answer 4

Loss of amino acid

Question 5

What happens to the protein in the majority of people with CF?

Answer 5

They make the protein but it doesn’t get to the plasma membrane

Question 6

What functions do membrane proteins have?

Answer 6

• receptors
• transporters
• channels
• structural
• enzymes
• markers

Question 7

What is the definition of a membrane protein as a receptor?

Answer 7

A protein that receives a ‘signal’ (usually a chemical) and sets in place events that end up with a response to that signal

Question 8

What is the example of rhodopsin?

Answer 8

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

Question 9

Definition of membrane protein as a transporter

Answer 9

A protein that regulates the flux/flow/import/export/transport of chemicals from one side of a biological membrane to the other

Question 10

What is the example of GLUT-4 as a transporter?

Answer 10

collects glucose from outside the cell when its in high concentrators and brings it inside the cell

Question 11

Definition of membrane proteins as ion channels

Answer 11

A protein which opens up a continuous pore through the membrane through which ions flow according to their concentration gradient

Question 12

Why are transporters and channels different?

Answer 12

A channel can be open all the way through unlike a transporter

Question 13

What is quicker, a transporter or a channel?

Answer 13

Channels are far quicker than transporters as they are purely limited by diffusion rate

Question 14

What is an example of membrane proteins as markers?

Answer 14

The example of MHC with infection

Question 15

What are the three different categories of membrane proteins?

Answer 15

Integral membrane-spanning
Peripheral membrane-attached
Anchored

Question 16

What parts of the peripheral protein are hydrophilic/phobic?

Answer 16

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

Question 17

What sort of protein might have a hydrophilic core and still sit in a membrane?

Answer 17

Channels generally form structures with a hydrophobic outside and hydrophilic inside

Question 18

Porins… what is the size controlled by?

Answer 18

Number of strands (think of a barrel, planks of wood round the barrel)

Question 19

Are strands around porins usually an even or odd number?

Answer 19

Even number (at least 9, as many as 22)

Question 20

Why do porins tend to have even numbers of strands?

Answer 20

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.

Question 21

Are membrane spanning regions predictable for alpha helices and beta sheets?

Answer 21

Alpha helices - yes

Beta sheets - no

Question 22

What is the concept of a hydrophobicity scale?

Answer 22

Each amino acid has a given likelihood of being in a membrane spanning region of a protein

Question 23

How does a hydrophobicity profile work?

Answer 23

• 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

Question 24

What would be the prediction if a protein had 7 big hydrophobic areas?

Answer 24

It has 7 transmembrane regions