Sulfated Glycoconjugates

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Presentation transcript:

Sulfated Glycoconjugates Biosynthesis, Control, and Regulation

Regulation Glycobiology What do we know? Complex mechanism of regulation Ongoing research What do we know? Proteoglycans require O-linked glycosylation Biosynthesis occurs in ER and GA Tetrasaccharide linkage unique to proteoglycans Unique linear, unbranched Glycosaminoglycan (GAG) Sulfation and other modifications occur at the end of proteoglycan synthesis

Proteoglygan structure

Route of proteoglycan synthesis

Tetrasaccharide linkgage

UDP-GlcA Transferase I Mechanism

Heparan Sulfate/Heparin

Heparan Sulfate/Heparin Know sulfation mechanism, catalyze the inversion of stereochemistry in biological molecules

Chondroitin Sulfate/Dermatan Sulfate

Keratan Sulfate

Ongoing Research Still unclear: How serine is selected What factors determine how long GAG chains polymerize Organization of the enzymes of the GA compartment and how they are regulated

References Kusche-Gullberg, Marion. Kjellén, Lena “Sulfotransferases in glycosaminoglycan biosynthesis” Current Opinion in Structural Biology. Volume 13, Issue 5, October 2003, 605-611 Prydz1, Kristian. Dalen, Knut Tomas. “Synthesis and sorting of proteoglycans” Journal of Cell Science 113, 193-205 (2000) Aberts, Bruce. Johnson, Alexander. Lewis, Julian. Raff, Martin. Roberts, Keith. Walter, Peter.“Molecular Biology of The Cell” 5th edition. 2008

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