Membrane proteins & carbohydrates

Question 1

Define dementia

Answer 1

An umbrella term for serious deterioration in mental functions

Question 2

What are the 4 As and one V for Alzheimers symptoms

Answer 2

Amnesia
Aphasia (language problems)
Agnosia (recognition problems)
Apraxia (difficulty in complex tasks)
Visuospatial difficulties

Question 3

What is the cause of Alzheimers?

Answer 3

Nerve cells in the brain dying and connections degenerating so normal communication is lost.
The short peptide amyloid-beta (Abeta) proteolytically cleaved from the larger membrane bound amyloid precursor protein (APP), this then forms senile plaques in the brain.
Chemical and electrical signalling goes wrong and neurones eventually die. The brain shrinks and less glucose is metabolised.

Question 4

Name 2 drugs currently used to relieve Alzheimers symptoms

Answer 4

Cholinesterase inhibitors
NMDA receptor antagonists
anti-psychotic drugs

Question 5

What is the connection between alzheimers and cholesterol?

Answer 5

The apolipoprotein E4 involved in cholesterol transport is more prevalent in AD patients
AD prevalence is 70% lower in people taking statins because statins lower A beta production in cells, altering cholesterol content and fluidity of membrane rafts

Question 6

Where are integral (transmembrane) proteins based in the membrane?

Answer 6

They go right the way through, interacting with both the hydrophobic fatty acid chains and the hydrophilic exterior

Question 7

What amino acids do integral membrane proteins predominantly contain?

Answer 7

Was with hydrophobic side chains because they are held int he membrane through hydrophobic interactions

Question 8

How can integral membrane proteins be removed from the membrane? Why?

Answer 8

Organic solvents or detergents

Because they are held in through hydrophobic interactions

Question 9

What are the 3 domains of the integral membrane protein Glycophorin?

Answer 9

Hydrophilic domain which is glycoslated, on the extracellular side
Hydrophobic transmembrane domain which forms an alpha helix
Hydrophilic domain in the cytosol

Question 10

What is special about the integral membrane protein Bacteriorhodopsin?

Answer 10

has 7 transmembrane helices embedded in the hydrophobic interior of the bilayer with short loops on either side of the membrane, has an antiparallel orientation

Question 11

Where are lipid linked proteins found on the membrane? how are they attached?

Answer 11

Attached to the edge through DIRECT COVALENT INTERACTION between lipids and the fatty acid on the protein (so they are called lipid modified, or acylated)

Question 12

Give the four types of modifications of lipid linked membrane proteins

Answer 12

Glycosyl-phsphatidylinositol (GPI) anchoring
Myristoylation
Prenylation
Palmitoylation

Question 13

Define Glycosyl-phosphatidylinositol (GPI) anchoring? In which proteins does it occur? Give an example

Answer 13

Occurs in SECRETORY proteins, they have a C terminal sequence that is recognised by enzymes which add the GPI anchor to the extracellular surface of the protein’s membrane and cleave the amino acids off. The protein is released into the extraceullar space and the rest is anchored outside the cell. e.g. Prion protein in BSE

Question 14

Define Myristoylation? which proteins is this in?

Answer 14

Typically in SIGNALLING and VIRAL proteins

A myristate group is added. can be anchored inside or outside the cell

Question 15

Define prenylation. Give two example signalling proteins where this occurs

Answer 15

A lipid “anchor” is attached to a protein, specifically a farnesyl or geranylgeranyl lipid chain is attached to a protein, which then serves to anchor the protein to the intracellular face of the membrane. This occurs at Cysteine redisude e.g. Ras, Rho, insulin receptors

Question 16

Define palmitoylation

Answer 16

Palmitoyl fatty acids are attached anywhere in the protein where there is a cysteine in the right context

Question 17

Where are peripheral membrane proteins located? What bonds do they form with the membrane?

Answer 17

On the outside of the membrane; they interact only with the lipid head groups through IONIC INTERACTIONS

Question 18

How can peripheral membrane proteins be removed from the membrane?

Answer 18

Ionic interactions can be disrupted with a high sat (Na+cl-) solution, which washes the proteins off in a soluble form

Question 19

Give two examples of peripheral membrane proteins. What type of proteins are these?

Answer 19

Spectrin and actin

Cytoskeletal (gives shape)

Question 20

What is the role of cytoskeletal peripheral membrane proteins such as spectrin and actin?

Answer 20

They form a SCAFFOLD on the cytosolic side of the membrane, attached to integral membrane proteins. This helps to maintain the shape of the cells and restricts the lateral movement of the integral membrane proteins

Question 21

Why is the removal of peripheral membrane proteins from red blood cells such a problem? What are hereditary spherocytosis and elliptocytoisis caused by?

Answer 21

It causes loss of the rigid shape as they are cytoskeletal proteins and allows the membrane proteins to become laterally mobile, which can result in abnormally shaped blood cells which are degraded more rapidly by the spleen
Caused by mutations in genes encoding sectarian or ankyrin proteins

Question 22

Name three molecules that lipid rafts are rich in

Answer 22

cholesterol
gylcosphingolipids
sphingomyelin
certain proteins

Question 23

Why are lipid rafts important in Alzheimers disease?

Answer 23

The proteolytic processing of APP in cholesterol rich lipid rafts produces the toxic amyloid beta peptide which forms senile plaques in the brain, whereas cleavage of APP in other parts of the membrane prevent the formation of amyloid-beta
Modulation of the membrane structure may influence the production of amyloid-beta and progression of ALzheimers

Question 24

What is the role of carbohydrates (sugars) on the lipids (glycolipids) and proteins (glycoproteins) in the membrane?

Answer 24

Stabilising proteins and intercellular recognition

Question 25

What is an O linked sugar? How long are these?

Answer 25

The sugar is attached to the hydroxyl group in the side chain of serine or threonine residues in proteins
These are often short, only 2-5 sugars

Question 26

What are N-linked sugars?

Answer 26

Sugars are attached to the side chain of asparagine residues in proteins, but only in the sequence Asn-X-Ser/Ther (where X is NOT Pro)
These are large branched structures with as many as 30-40 sugar residues

Question 27

What is an example of an N-linked sugar?

Answer 27

ABO blood grouping