Proteoglycans and glycoproteins

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

Transcript of Proteoglycans and glycoproteins

Page 1: Proteoglycans and glycoproteins

Proteglycans and Glycoproteins

BSBT 513Metabolism and Metabolomics

Presented bySakshi Saxena

ASU2013010200124IBT VIth sem

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EXTRACELLULAR MATRIX

GAGs Proteoglycans Glycoproteins

www.protein.osaka-u.ac.jp

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EXTRACELLULAR MATRIX

GAGs Proteoglycans Glycoproteins

www.protein.osaka-u.ac.jp

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PROTEOGLYCANAND

GLYCOPROTEIN

www.scienceisdelicious.net

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

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

downhousesoftware.wordpress.com

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Proteoglycans = GAGs + Core proteinsThe GAGs extend perpendicularly from the core in a brush-like structure.

STRUCTURE OF PROTEOGLYCAN

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STRUCTURE OF PROTEOGLYCAN

themedicalbiochemistrypage.org

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STRUCTURE OF PROTEOGLYCANThe 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

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STRUCTURE OF PROTEOGLYCANThe 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.

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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

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EXAMPLES1. 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

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EXAMPLES2. 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

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EXAMPLES3. 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.

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EXAMPLES4. 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

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EXAMPLES5. 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

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GLYCOPROTEINS

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INTRODUCTIONGlycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains.

The attachment process is called glycosylation and is between

a. the hydroxyl (-OH) group of the R group of serine or threonine - called "O-linked"

b. 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.

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INTRODUCTION

www.biology-pages.info

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N- & O-LINKED GLYCOPROTEINS

oregonstate.edu

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EXAMPLES

Dental Biochemistry ; Lecture 45 Carol Lutz, PhDComplex Carbohydrates: Glycoproteins and Proteoglycans

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EXAMPLES1. 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.

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EXAMPLES2. 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

chainsAsp

2 sialic acid

2 galactose

3 mannose

4GlcNac

Amide linkage

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EXAMPLES3. 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

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EXAMPLES4. 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.

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What’s the difference?

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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.

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1. Proteoglycans : written by: ruth steer from manchester university. Accessed from http://www.Fastbleep.Com/biology-notes/31/179/1026

2. GLYCOPROTEINS: AN OVERVIEW M SHYLAJA and H S SESHADRI accessed from http://onlinelibrary.Wiley.Com/doi/10.1016/0307-4412(89)90136-2/pdf

3. STRUCTURE AND FUNCTION OF TRANSFERRIN M CHING-MING CHUNG. Accessed from http://onlinelibrary.Wiley.Com/doi/10.1016/0307-4412(84)90118-3/pdf

4. Aggrecan and Versican accessed fom http://www.glycoforum.gr.jp/science/word/proteoglycan/PGA03E.html

5. Proteoglycans accessed from http://www.cryst.bbk.ac.uk/pps97/assignments/projects/emilia/Proteoglycans.HTM

REFERENCES

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6. Structural Biochemistry/Carbohydrates/Proteoglycans accessed from https://en.wikibooks.org/wiki/Structural_Biochemistry/Carbohydrates/Proteoglycans

7. Glycosaminoglycans accessed from http://themedicalbiochemistrypage.org/glycans.php

8. 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.

REFERENCES

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