Membrane Proteins

Which of the following are the main classes of integral membrane proteins

Type 1 & II One transmembrane segment Type III Multiple transmembrane segments in one polypeptide chain Type IV Multiple transmembrane segments from different polypeptide chains forming a channel Type V Lipid-linked membrane proteins Type VI Lipid-linked proteins and transmembrane segments

An integral membrane protein can be extracted with:

a solution containing detergent

Following exposure to a hormone, cells typically become desensitised to the hormone signal for 5-10 minutes following which their sensitivity to the hormone returns. A likely molecular explanation for this observation is:

receptor-mediated down regulation of hormone-receptor complex

Receptor mediated endocytosis

is involved in receptor recycling; involves cell membrane fusion; can involve the protein clatherin; can induce a refractory period for signal transduction

The glycocalyx is:

combination of glycoproteins and glycolipids that protrude from the external surface of the plasma membrane

The type of motion least common in biological membranes is:

flip-flop diffusion of phospholipid from one monolayer to the other

The lipid environment of the lipid membrane can affect membrane bound proteins in one, or more, of the following ways: i. topology ii. conformation iii. lateral diffusion through membrane iv. constrain protein folding

i, ii, iii, and iv

The differences between peripheral and integral membrane proteins are that:

Peripheral membrane proteins lack discrete hydrophobic regions; peripheral membrane proteins are not located within the lipid membrane; peripheral membrane proteins are easily extracted by changes in pH or ionic strength; peripheral membrane proteins associate with membranes though electrostatic forces, van der Waals forces, and hydrogen bonds

Which of these statements about the composition of membranes is generally true?

The inner and outer membranes of mitochondria have different protein compositions

When biological membranes are viewed with an electron microscope after freeze-fracturing, one sees particles of various sizes standing out against a smooth background. Which of these statements is correct?

The particles are individual proteins or protein complexes.

Peripheral membrane proteins

are generally noncovalently bound to membrane lipids

Membrane proteins:

are sometimes covalently attached to lipid moieties; are sometimes covalently attached to carbohydrate moieties; are composed of the same 20 amino acids found in soluble proteins.

The diagram below shows the formation of a mouse-human hybrid cell. Inspect the diagram carefully and then select the most appropriate answer that best describes a characteristic of the membrane illustrated by the diagram

membrane fluidity

The general types of membrane proteins are:

peripheral proteins, integral proteins, and lipid anchored proteins

A hydropathy plot is used to:

predict whether a given protein sequence contains likely membrane-spanning segments

Hydrophobic residues are seen on the 'outside' surface of transmembrane proteins (i.e. orientated towards the lipid bilayer of the membrane). Consequently, it was suggested that the transmembrane proteins have an 'inside-out' structure compared with a globular protein. Why was this suggestion proposed?

Globular proteins are seen to have hydrophobic residues inside the core of the protein. Globular proteins have an inner hydrophobic core which seemed to contrast with transmembrane proteins which had a hydrophobic external surface. However, it has been seen that even transmembrane proteins have a hydrophobic core and so the description of a transmembrane structure being 'inside out' compared with globular proteins is incorrect.

The diagram below shows part of a transmembrane protein. The yellow coloured L subunit has a disordered loop within the hydrophobic core of the lipid membrane. Does this then invalidate the general rule that transmembrane proteins span the lipid bilayer as alpha helices or beta sheets? Explain

It does not invalidate the general rule because the helix is still apparent and the loop does not completely 'span' the membrane. The loop can exist in a lipid environment if it contains hydrophobic or non-polar residues. However it does show that there may be other potential ways for the protein to fold within a membrane that we don't yet appreciate because the structure of so few transmembrane proteins are known

Glycophorin is a heavily glycosylated protein found on the red cell membrane. One or more of the statements in the following list may apply to this protein:

It is a Type I membrane protein; The carbohydrate composition of the protein gives the red cell a hydrophilic surface which allows them to circulate without 'sticking' to other cells or vessel walls

In the membrane of a human red blood cell the ratio of the mass of protein to phospholipd to cholesterol is about 2:1:1. How many lipid molecules (phospholipid and cholesterol) are there for every protein molecule? (The average molecular weights of a protein = 50,000, phospholipid = 800, and cholesterol = 386). Hint: choose any number for the 'mass' for the membrane.

96. Choose a 'mass' for the membrane say 100,000 thus the protein would be 2/4 of that mass, phospholipid would be 1/4 of that mass, and cholesterol would be 1/4 of that mass. Hence • 100,000 x 2/4 = 50,000 if average protein = 50,000 then this is one protein molecules • 100,000 x 1/4 = 25,000 if average phospholipid = 800 then this is about 31 phospholipid molecules • 100,000 x 1/4 = 25,000 if average cholesterol = 386 then this is about 65 cholesterol molecules • Total phospholipid and cholesterol = 96 or about 100 lipids for every one protein.

What kind of molecule is a SNARE, what general types are there, and what is its function?

A SNARE is a protein required for receptor-mediated membrane fusion. The acronym is for: Synaptosome associated protein receptors There are two types of SNARES: vSNARES and tSNARES The vSNARES are on vesicle (v) and the tSNARES are on the target membrane (t). The interaction of v and t SNARES instigate the membrane fusion event.

Explain why the polypeptide chain of a transmembrane protein usually crosses the lipid bilayer as either an alpha helix or a beta barrel. You need to include the characteristics of each of these structures in your answer.

A helix is a regular (geometric) secondary structure made from within the same part of the polypeptide chain. The side chains of the residues making up the structure are oriented out from the centre of the helix. If these side chains are non-polar then the helix would be able to sit within the hydrophobic, non-polar, fatty acids of the membrane. Additionally, all of the polar backbone groups (i.e. amide nitrogen -NH and carbonyl oxygen C=O) can be matched by hydrogen bonds, within the helix structure, that effectively prevent these polar groups from potentially disrupting interactions with the non-polar fatty acids of the membrane. A beta barrel is a supersecondary structure made from beta strands that are non-covalently associated with other in the shape of a barrel. The beta strands are from different parts of the polypeptide chain and are usually antiparallel to each other. It is necessary to form a barrel structure so that all of the polar backbone groups (i.e. amide nitrogen -NH and carbonyl oxygen C=O) can be matched by hydrogen bonds that effectively prevent these groups from potentially disrupting interactions with the non-polar fatty acids of the membrane. Additionally, the side chain groups (which are oriented both above and below the plane of the strand) would tend to be non-polar on the 'outside' of the barrel so that the structure can sit within the hydrophobic, non-polar, fatty acids of the membrane.

What useful information can you derive from the protein/lipid ratio of the following?nerve cell plasma membrane 0.23inner mitochondrial membrane 3.54

A. Nerve cell plasma membrane requires relatively more lipid that the inner mitochondrial membrane for its function B. Nerve cell plasma membrane probably use the lipid as insulation C. The inner mitochondrial membrane is probably involved in considerable metabolic activity D. The nerve cell plasma membrane and the inner mitochondrial membrane have widely different functions.

Receptor mediated endocytosis:

A. is involved in receptor recycling B. involves cell membrane fusion C. can involve the protein clatherin D. can induce a refractory period for signal transduction

Which of the following is true regarding single pass transmembrane proteins?

Contain only one hydrophobic segment. Option A is incorrect because single pass transmembrane proteins only traverse the membrane once, option A refers to characteristics of multi pass proteins. (Slide 14 of Membrane Protein lecture).Option B is incorrect because multi pass proteins contain 2-20 hydrophobic segments, not single pass proteins. (Also slide 14).Option C is incorrect because transmembrane proteins protrude from both sides of the membrane, monotopic integral proteins only protrude from one side of the membrane. (Slide 10).Option D is incorrect because single pass transmembrane proteins are comprised of mostly hydrophobic alpha-helices and some beta-sheet structures, not the other way around. (Slide 11).Therefore option E is correct, single pass transmembrane proteins contain only one hydrophobic segment. (Slide 11).

It has been suggested that transmembrane proteins have an 'inside-out' structure compared with a globular protein. Give reasons for this suggestion based upon your knowledge of membrane proteins and general protein structure.

Globular proteins generally have an inner hydrophobic core and an external hydrophilic surface. This allows globular proteins to be soluble within an aqueous environment. This seems to contrast with transmembrane proteins which are generally seen to have a 'hydrophobic exterior' and a 'hydrophilic interior'. The 'hydrophobic exterior' of a transmembrane protein refers to the outward orientation of hydrophobic side chains from the surface of a beta barrel or alpha helix bundle structure within the protein. This allows the protein to interact with the lipids in the lipid bilayer of the membrane. The 'hydrophilic interior' of the transmembrane protein refers to presence of hydrophilic side chains on the inside surface of the the beta barrel or alpha helix bundle structures. This would allow some transmembrane proteins to act as channels or carriers of aqueous solutes (molecules or ions) within a hydrophobic environment of the lipid membrane. Consequently, given these descriptions transmembrane proteins may be seen as having an 'inside-out' structure compared with globular proteins. However, it should be noted that transmembrane proteins can also have hydrophobic interior surfaces of beta barrel structures or alpha helix bundles.

Epithelial cells form tightly cohering sheets whereas erythrocytes occur as single cells. What type of integral proteins would you expect to reside in the plasma membrane of an epithelial cell that might be absent from that of an erythrocyte?

proteins involved in cell-cell adhesion or cell-cell communication. the tightly cohering cells would definitely need effective cell to cell adhesion or communication for the epithelial cells to adhere into cohering sheets of cells. Erythrocytes because they exist a 'single cells' would probably not require too many of these types of proteins.