JA - Glycobiology Flashcards
(14 cards)
What are features of antibodies and viruses related to glycobiology?
Antibodies are glycoproteins and are hugely important biotherapeutics
Viruses can use glycosylation to hide from the immune system
- Glycans cover some of the surface of the protein
What does glycobiology include the study of? (5)
- The chemistry of carbohydrates
- The enzymology of glycan formation and degradation
- The recognition of glycans by specific proteins (lectins)
- Roles of glycans in complex biological systems
- Their analysis or manipulation by various techniques.
What are the 3 major functions of glycans?
- Perform key structural roles
- Important in intrinsic or “self” recognition
- Important in the identification of foreign pathogens/ signals, extrinsic recognition
What are some common monosaccharide units found in glycoconjugates? (6)
Pentoses: five-carbon neutral sugars
- D-xylose (Xyl)
Hexoses: six-carbon neutral sugars
- D-glucose (Glc)
Hexosamines: hexoses with an amino group at the 2-position
- N-acetyl-D-glucosamine (GlcNAc)
6-Deoxyhexoses:
- L-fucose (Fuc)
Uronic acids: hexoses with a carboxylate at the 6-position
- D-glucuronic acid (GlcA)
Nonulosonic acids: family of nine-carbon acidic sugars
- Sialic acid N-acetylneuraminic acid (Neu5Ac, also sometimes called NeuAc or, historically, NANA)
What linkage is found in humans vs insects?
Linkage found on almost every glycoprotein in humans
- α(1→6) linked
Linkage found in insects
- α(1→3) linked
Describe the 3 stages of N-linked glycan attachment and processing
Stage 1: Synthesis of lipid-linked precursor oligosaccharide
Stage 2: En bloc transfer to the protein and the role of glycans in protein folding
Stage 3: Increasing complexity of glycan processing
What occurs in Stage 1- Synthesis of lipid-linked precursor oligosaccharide? (3)
- N-linked glycan biosynthesis begins in the cytoplasm
- The glycan is assembled on a lipid attached to the membrane, dolichol phosphate
- During biosynthesis, the precursor is flipped into the ER lumen
What occurs in Stage 2: En bloc transfer to the protein and the role of glycans in protein folding? (3)
- Glucosylated N-linked glycans act as a signal to the cell that the protein is not correctly folded
- UGGT will add glucose back to glycans of misfolded proteins
- Persistently misfolded proteins are degraded
What does the precise composition of the fully processed glycan depend on? (4)
- Enzyme expression levels of the producer cell
- Metabolic state of the cell
- The structure of the protein
- Stress responses/ activation, e.g. cytokines
What are 3 features of O-linked glycans?
- O-linked glycans do not have a consensus sequence and cannot be predicted to attach
- O-linked glycans are enriched in flexible loops, and Ser-Thr-Pro are often O-glycosylated
- Mucin domains are heavily O-glycosylated
Some functions of O-linked glycans (3)
- O-GalNAc sugars help increase rigidity of the region close to the membrane so that a glycoprotein can extend outwards
- E.g. the low-density lipoprotein receptor (LDLR) is projected from the cell surface by a region rigidified by O-glycans.
- This promotes binding of the LDLR to LDL, which LDLR transports the LDL particle into the cell where the cholesterol is used
What does the ebola glycoprotein contain?
A mucin domain that helps it avoid antibodies
3 features of blood group antigens related to glycobiology
- Antigens on red blood cells and other cells determine an individual’s blood group.
- Blood group antigens are found on N-glycoproteins, O-glycoproteins, and glycolipids.
- Antibodies circulating in can recognize foreign blood group antigens and can result in severe immune responses, crucial in transplantation and blood transfusion.
What antibodies and antigens are present in the 4 blood groups?
Blood group A:
- Anti-B
- A antigen
Blood group B:
- Anti-A
- B antigen
Blood group AB:
- No antibodies in plasma
- A and B antigens
Blood group O:
- Anti-A and Anti-B
- No antigens in RBC
