Proteoglycans and glycoproteins

The presentation deals with structure and functions of Proteoglycans and glycoproteins

1. Proteglycans and Glycoproteins BSBT 513 Metabolism and Metabolomics Presented by Sakshi Saxena ASU2013010200124 IBT VIth sem

2. Extracellular matrix GAGs Proteoglycans Glycoproteins www.protein.osaka-u.ac.jp

3. Extracellular matrix GAGs Proteoglycans Glycoproteins www.protein.osaka-u.ac.jp

4. Proteoglycan And Glycoprotein www.scienceisdelicious.net

5. Introduction Proteoglycans are complex extracellular macromolecules consisting of a multidomain core protein to which is attached one or more glycosaminoglycan (GAG) chains.

6. Introduction Proteoglycans are complex extracellular macromolecules consisting of a multidomain core protein to which is attached one or more glycosaminoglycan (GAG) chains. downhousesoftware.wordpress.com

7. Proteoglycans = GAGs + Core proteins The GAGs extend perpendicularly from the core in a brush-like structure. Structure of Proteoglycan downhousesoftware.wordpress.com

8. Structure of Proteoglycan themedicalbiochemistrypage.org

9. Structure of Proteoglycan The linkage of GAGs to the protein core, in most but not all proteoglycans , involves a specific tetrasaccharide linker : two galactose (Gal) residues, and a xylose ( Xyl ) residue forming a structure such as: GAG (n) – GlcA –Gal–Gal– Xyl –Ser–protein. themedicalbiochemistrypage.org

10. Structure of Proteoglycan The linkage of GAGs to the protein core, in most but not all proteoglycans , involves a specific tetrasaccharide linker : two galactose (Gal) residues, and a xylose ( Xyl ) residue forming a structure such as: GAG (n) – GlcA –Gal–Gal– Xyl – Ser –protein.

11. Structure of Proteoglycan Some GAGs are linked to the protein core of proteoglycans via a trisaccharide linkage that lacks the GlcA residue. www.cryst.bbk.ac.uk

12. Examples 1. Syndecans Syndecans constitute a family of transmembrane proteoglycans that perform multiple functions during development, damage repair, tumor growth, angiogenesis, and neurogenesis . The extracellular domain of syndecans sheds periodically from the cell membrane. This process may be stimulated in response to inflammation, tissue damage, and other pathological manifestations. Cleaved domain may act as either competitive inhibitor or activator of signaling cascades www.glycoforum.gr.jp

13. Examples 2. Glypicans Glypicans are  heparin sulfate  proteoglycans involved mainly in regulation of growth factor signalling - Wnt , Hhs (Hedgehogs), FGF (Fibroblast growth factor), BMP (bone morphogenic protein). Extracellular globular domain. Can be shed into the extracellular environment. Largely through action of the extracellular lipase which cleaves the GPI anchor. www.glycoforum.gr.jp

14. Examples 3. Aggrecans Aggrecan is a critical component for cartilage structure and the function of joints . The synthesis and degradation of aggrecan are being investigated for their roles in cartilage deterioration during joint injury, disease, and aging www.sigmaaldrich.com It contains three globular domains, G1, G2, and G3 that are involved in aggregation, hyaluronan binding, cell adhesion, and chondrocyte apoptosis. This structural molecule produces a rigid, reversibly deformable gel that resists compression.

15. Examples 4. Lumican Lumican is a  proteoglycan  member of the small leucine -rich proteoglycan (SLRP) family which is a major  keratan sulfate  proteoglycan  of the cornea and is involved in collagen fibril organization and circumferential growth, corneal transparency, and epithelial cell migration and tissue repair. There are four N-linked sites within the leucine -rich repeat domain of the protein core that can be substituted with  keratan sulfate. The core protein of lumican (like  decorin  and  fibromodulin ) is horseshoe shaped. onlinelibrary.wiley.com

16. Examples 5. Perlecan Perlecan is a large   heparan sulfate proteoglycan multidomain (five domains, labeled I-V)  proteoglycan  that binds to and cross-links many extracellular matrix (ECM) components and cell-surface molecules   Perlecan is a potent inhibitor of smooth muscle cell proliferation and is thus thought to help maintain vascular homeostasis. Perlecan can also promote growth factor (e.g., FGF2) activity and thus stimulate endothelial growth and re-generation. www.ijdr.in

17. Glycoproteins

18. Introduction Glycoproteins  are proteins that contain oligosaccharide chains ( glycans ) covalently attached to polypeptide side-chains. The attachment process is called glycosylation and is between the hydroxyl (-OH) group of the R group of serine or  threonine  - called " O-linked " the amino group (-NH2) in the R group of  asparagine  - called " N-linked ". Other attachments (rare) are In  P- glycosylation , sugars are attached to phosphorus on a  phosphoserine . In  C- glycosylation , sugars are attached directly to carbon, such as in the addition of mannose to tryptophan.

19. Introduction www.biology-pages.info

20. N- & o-linked glycoproteins oregonstate.edu

21. Examples Dental Biochemistry ; Lecture 45 Carol Lutz, PhD Complex Carbohydrates: Glycoproteins and Proteoglycans

22. Examples 1. Mucin Mucins  are a family of high molecular weight, heavily  glycosylated   proteins  ( glycoconjugates ) produced by epithelial tissues physrev.physiology.org Mucins' key characteristic is their ability to form gels; therefore they are a key component in most gel-like secretions, serving functions from lubrication to cell signaling to forming chemical barriers.

23. Examples 2. Transferin Transferrins  are iron-binding blood plasma  glycoproteins  that control the level of free iron in biological fluids. Transferin Proteins Carbohydrate Amino acids 2 Identical branched Heteropolysaccharide chains Asp 2 sialic acid 2 galactose 3 mannose 4GlcNac Amide linkage

24. Examples 3. Fibrinogen Fibrinogen (factor I) is a glycoprotein in vertebrates that helps in the formation of blood clots. It is composed of three pairs of polypeptides: two Aa , two Bb, and two g.   These polypeptides are linked together by 29 disulphide bonds with polypeptides oriented so all six N-terminal ends meet to form the central E domain.   www.ebi.ac.uk

25. Examples 4. FSH 5. EPO Follicle-stimulating hormone (FSH) is a glycoprotein polypeptide hormone.  It is a heterodimer , consisting of two polypeptide units, alpha and beta.  The sugar portion of the hormone is covalently bonded to   asparagine , and is composed of N- acetylgalactosamine , mannose, N- acetylglucosamine ,   galactose , and sialic acid. It regulates the development, growth, pubertal maturation and reproductive processes of the human body. Erythropoeitin (EPO) is a hormone consisting of 193 amino acids in humans providing a molecular weight of 34,000.  It is highly  glycosylated  (40% of total molecular weight) and is responsible for production of RBCs. kimbuttbiol4450.blogspot.in

26. What’s the difference?

27. Proteoglycans Glycoproteins Carbohydrate chains are negatively charged due to the presence of sulfate and uronic acid groups Carbohydrate chains may or may not be negatively charged Glycoproteins are found mainly in cellular membranes. Proteoglycans are found mainly in connective tissues. • Proteoglycans are important in modulation of cellular development processes Glycoproteins function in cellular recognition.

28. Proteoglycans : written by: ruth steer from manchester university. Accessed from http://www.Fastbleep.Com/biology-notes/31/179/1026 GLYCOPROTEINS: AN OVERVIEW M SHYLAJA and H S SESHADRI accessed from http://onlinelibrary.Wiley.Com/doi/10.1016/0307-4412(89)90136-2/pdf STRUCTURE AND FUNCTION OF TRANSFERRIN M CHING-MING CHUNG. Accessed from http://onlinelibrary.Wiley.Com/doi/10.1016/0307-4412(84)90118-3/pdf Aggrecan and Versican accessed fom http://www.glycoforum.gr.jp/science/word/proteoglycan/PGA03E.html Proteoglycans accessed from http://www.cryst.bbk.ac.uk/pps97/assignments/projects/emilia/Proteoglycans.HTM R E F E R E N C E S

29. Structural Biochemistry/Carbohydrates/ Proteoglycans accessed from https://en.wikibooks.org/wiki/Structural_Biochemistry/Carbohydrates/Proteoglycans Glycosaminoglycans accessed from http://themedicalbiochemistrypage.org/glycans.php Carbohydrate Structure of Human Fibrinogen R. Reid Townsend&, E. Hilliker ‘, Yu- Teh Li&, Roger A. Lainefg , William R. Bellah , and Yuan Chuan Lee 9. GLYCOPROTEINS: AN OVERVIEW M SHYLAJA and H S SESHADRI accessed from THE JOURNAL OF BIOLOGICAL CHEMISTRY Prrnted rn [J.S.A Vol. 257. No. 16, Iswe of August 25. R E F E R E N C E S