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Chapter 11

BCM 475 Chapter Notes - Chapter 11: Glycosaminoglycan, Glycoprotein, Glycosylation


Department
Biochemistry
Course Code
BCM 475
Professor
Welch
Chapter
11

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GLYCOPROTEINS | Carbs linked to proteins
- Glycosylation increases proteome complexity
o Protein with numerous glycosylation sites can have different glycosylated forms
Ex. Proteoglycan in matrix of cartilage
- Composed of:
o Aggrecan: shock absorber
o Collagen: triple helix for tensile strength/structure
- Aggrecan molecules are noncovalently bound to long filament (link together molecules of glycosaminoglycans)
o Water binds to glycosaminoglycan (attracted to charges)
- Absorbed water allows cushioning properties
o Exert force water is squeezed out
o Release pressure water rebinds
Mucins,
Mucoproteins
Mostly carbs (80%)
N-Acetylgalactosamine (amino sugar) glycosylates serine/threonine residues to protein
Lubricant (mucus), hydrate and protect underlying cells
Synthesized by specialized cells in tracheobronchial, gastrointestinal, genitourinary tracts)
Capable of forming large polymeric structures
Protein backbone (variable number of tandem repeats region VNTR) rich in serine/threonine
residues that are O-glycosylated
LINKAGE
- Potential glycosylation sites can be detected within amino acid sequences
o Which sites are glycosylated depends on protein structure and cell type (where protein is expressed)
N-linkage: Sugars in glycoproteins attached to amide N atom in side chain of asparagine
o Common pentasaccharide core with 3 mannose and 2 N-Acetylgalactosamine residues
Additional sugars variety
O-linkage: Sugars in glycoproteins attached to O atom in side chain of serine/threonine
Glycoproteins
Protein constituent is largest component
(weight)
Many proteins secreted from cells are
glycosylated
Functions:
- Component of cell membrane (cell
adhesion, binding sperm-egg)
- Linking carbs to soluble proteins
Ex. Glycoprotein hormone erythropoietin (EPO)
- Secreted by kidneys, stimulates production of
RBCs
- N-glycosylated at 3 Asp and O-glycosylated at 1
Ser
- 40% carbs; glycosylation enhances protein stability
Recombinant human EPO = treatment of anemia
Proteoglycans
Protein component is conjugated to a polysaccharide (glycosaminoglycan)
Carbs are larger % by weight (glycosaminoglycan is 95% weight very polysaccharide-y
Many made of repeating disaccharide units
- At least 1 of 2 sugars has negatively charged carboxylate or sulfate group
Functions (determined by glycosaminoglycan part):
- Structural components, lubricants
- Mediates cell-matrix adhesion
Osteoarthritis
Proteolytic degradation of
aggrecan/collagen in cartilage
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