Glycoproteins

Question 1

If the sugars of glycoproteins are attached to an asparagine AA side chain, it is called?

Answer 1

N-linked oligosaccharides

Question 2

If the sugars of glycoproteins are attached to an oxygen in the side chains of hydrolyzed AAs serine, threonine, and hydroxylysine, they are called?

Answer 2

O-linked oligosaccharides

Question 3

How does the Ebola virus work?

Answer 3

the virus has an associated coat glycoprotein that binds preferably to endothelial cells, causing death of the cells and the resulting hemorrhaging. The virus also secretes a soluble glycoproteins that disrupts the functioning of neutrophils and macrophages responsible for cleaning up the infected endothelial cells. Thus, you get uncontrolled bleeding and eventually death

Question 4

What are glycoproteins?

Answer 4

a protein with a covalently attached carbohydrate. These tend to be lower in carb content, but the expression is variable

Question 5

What are proteoglycans?

Answer 5

glycoproteins with glycosaminoglycan (GAG) chains (usually attached by O-linked sugars). These tend to have high carb contents than standard glycoproteins

Question 6

T or F. almost all glycoproteins are extracellular, and most extracellular proteins are glycosylated

Answer 6

T

Question 7

Which extracellular proteins are not glycosylated?

Answer 7

albumin, an abundant serum transporter

Question 8

Where does N-linked glycosylation occur?

Answer 8

starts in the lumen in the ER and ends in the golgi

Question 9

What is the destiny of proteins made in the ER?

Answer 9

they are either going to face the lumen of the secretory pathway cellular components (i.e. ER or golgi) or they will secreted to the outside of the cell or face the outside of the cell. They won’t be cytoplasmic proteins

Question 10

When does N-linked glycosylation occur?

Answer 10

as the polypeptide is being synthesized

Question 11

How does N-linked glycosylation occur?

Answer 11

a preassembled oligosaccarhide is attached to the growing polypeptide via an Asn-X-Ser/Thr segment on the protein

Question 12

What segment of an oligosaccarhide facilities combining to the protein?

Answer 12

a dolichol phosphate group (removed after binding occurs). The N-linked protein is then altered as it moves through the ER and Golgi. Thus, all start the same but end products are very different

Question 13

What are two most common glycoproteins in the body?

Answer 13

collagen and fibronectin

Question 14

What is the role of fibronectin in the body?

Answer 14

it is a dimer of 2 similar subunits joined to together by disulfide bonds at the C terminus that have multiple functions including:

1) fibrin binding (the polymerized form that helps clot blood)
2) heparin binding (a proteoglycan)
3) cell binding (via cell-surface integrins)
4) collagen binding

can interact with all of these simultaneously if the domains are accessible (strings on a pearl)

note that there are three forms made by 1 gene via alternative splicing: a soluble form, a cell surface form, and a matrix form

Question 15

What are the functions of glycoproteins?

Answer 15

solubility and protection, RECOGNITION (tons of different ways)

Question 16

Are sugars hydrophilic or hydrophobic?

Answer 16

hydrophilic

Question 17

How does the soluble nature of glycoproteins help enzymes?

Answer 17

if the sugars (hydrophilic) of glycoproteins are lost, enzymes tend to aggregates and become insoluble

Question 18

How does the protective nature of glycoproteins help enzymes?

Answer 18

a cloud of sugars helps protect the protein from enzyme degradation (proteolysis) and loss of function

Question 19

How does sialic acid affect ceruloplasmin?

Answer 19

sugars can help maintain half-life

ceruloplasmin transports metals in the body and sialic acid on the sugars prevents binding of the protein to the galactose cell surface receptors in the liver, thus extending its half life and ability to function

-half life decreases by 700x if even 2 of the 10 sialic acid molecules are lost

Question 20

How can glycoproteins act as hormone receptors?

Answer 20

for example, beta-glycan is a transmembrane receptor for cytokine growth factor beta

Question 21

What is a common building block of N-linked oligosaccarhides?

Answer 21

mannose, N-acteyl glucosamine (both derivatized at the 2’ position), salic acid (derivatized at the 4’ position)

Question 22

What AA sequence is the basis of N-linked formation?

Answer 22

Asn*-X-Ser/Thr

Question 23

What do integrins do?

Answer 23

help in cell-matrix reactions that help maintain stability of the cell. Required for life. If a cell finds itself in the wrong atmosphere, it will undergo apoptosis

This is why you need to treat tissue plates with attachment molecules like integrin

Question 24

What do cadherins do?

Answer 24

they are calcium dependent adhesion molecules involved in making sure that different cell types (ex. liver vs. retinal) can find each other in the body and in development. Again, cells must be in a stable environment to liver

Question 25

How are glycoproteins involved in fertilization?

Answer 25

The ZP has glycoproteins that act as a barrier to sperm entry and sperm have gylactosyl transferases which can bind to the glycoproteins to initiate breaking it down. Following entry of one sperm, the ovum will make a stronger glycoprotein layer to prevent multiple fertilization

Question 26

What other functions are glycoproteins involved?

Answer 26

1) antigen presenting to T-lymphocytes requires glycoproteins
2) seletins on the cell surface of endothelial cells in vessels can recognize an infection outside of the cell, allowing the endothelial cell to express more selectins which cause white cells to bind to them, to be exocytosed from the bloodstream to the site of infection (called white-cell extravasation)- not a very well regulated process

Question 27

How can white-cell extravasation by controlled?

Answer 27

by limiting selectins on the endothelial cell surfaces..Because the inflammatory response of white cells can often be too much and cause damage to surrounding tissue, limiting selection expression can reduce the potential for damage to occur (common after an MI)

Question 28

What happens in I-cell disease?

Answer 28

enzymes need a phospho-mannose tag in order to be transported to lysosomes for degradative function of endocytose particles. In I cell disease, these enzymes are not given this glyco tag and are thus secreted from the cell, causing a buildup of material in the cell

Question 29

How does O-linked glycoproteins work?

Answer 29

one sugar is added at a time to a hydroxyl group on a protein using an activated UDP head group attached to each sugar