JA - Glycobiology Flashcards
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
