* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Extracellular Macromolecules
Cytokinesis wikipedia , lookup
Phosphorylation wikipedia , lookup
Magnesium transporter wikipedia , lookup
Protein (nutrient) wikipedia , lookup
Endomembrane system wikipedia , lookup
Protein folding wikipedia , lookup
Protein phosphorylation wikipedia , lookup
Protein domain wikipedia , lookup
G protein–coupled receptor wikipedia , lookup
Intrinsically disordered proteins wikipedia , lookup
Protein moonlighting wikipedia , lookup
Signal transduction wikipedia , lookup
Protein structure prediction wikipedia , lookup
Nuclear magnetic resonance spectroscopy of proteins wikipedia , lookup
Extracellular matrix wikipedia , lookup
Western blot wikipedia , lookup
Protein–protein interaction wikipedia , lookup
Extracellular Macromolecules Glycosaminoglycans; proteoglycans; glycoproteins; mucins Glycoprotein synthesis; plasma proteins Molecular immunology: innate immunity; inflammation Molecular immunology: adaptive (acquired) immunity Fibrous proteins: keratin, collagen and elastin Extracellular Macromolecules 1. Glycosaminoglycans Proteoglycans Glycoproteins Mucins Extracellular Macromolecules macromolecule % carb. glycosaminoglycans* (GAGs) proteoglycans* 90-95 glycoproteins 2-30 fibrous proteins 1-2 100 Examples of functions: mechanical supportlubrication cushioning adhesives cell spacers selective filters 1 * aka mucopolysaccharides, mucoproteins, respectively Extracellular matrix in tissues ground substance + fibers macromolecules between cells ground substance molecules GAGs/proteoglycans (mostly carbohydrate) – fibers fibrous proteins: structural epithelial cells adhesive • especially abundant in connective tissue adhesion molecules basal lamina extracellular matrix underlying cells 2 Adapted from Hypercell GAG structure A sugar exist as: independent molecules e.g., hyaluronate & heparin parts of larger structures e.g., in proteoglycans B sugar heteropolysaccharides repeating structure: disaccharide (AB)n ABABAB… where A is usually 1 uronic acid (hexose with C6 as COO– ) & B is 1 glycosamine (amino sugar) derivative unbranched glycosidic linkage anomeric C of 1 unit linked to hydroxyl of adjacent unit 3 GAG structure: repeating units GAG A sugar B sugar hyaluronate glucuronate N-acetyl glucosamine * 5 2 4 GAG structure: repeating units GAG A sugar 4 B sugar hyaluronate glucuronate N-acetyl glucosamine * chondroitin sulfate dermatan sulfate heparan sulfate heparin keratan sulfate 5 2 glucuronate N-Ac galactosamine 4-SO4 iduronate " glucuronate glucosamine N-SO3, 6-SO4 iduronate 2-SO4 " galactose N-Ac glucosamine 6-SO4 *opposite configuration in iduronate glucuronate/iduronate: epimers at C5 glucose/galactose: epimers at C4 Hyaluronate (aka hyaluronan) 5 mol wt: 106 – 107 (5000 – 50,000 monosaccharide units) very polar: 2 hydroxyls/unit 6 heteroatoms/unit COO– every other unit Display of HA binds cations: Na+, Ca++ in motion A B A B A B – – – 1 2 3 4 5 (glucuronate–N-acetyl glucosamine)3 (glcUA–glcNAc)3 6 6 Hyaluronate: structure & properties extended structure (charge repulsion) hydrophilic: binds 10 –100 × wt in H2O additional, loosely associated H2O, so that volume occupied ~1000 × weight Display of HA with glcUAs in CPK – – – 1 (glcUA–glcNAc)3 2 3 4 5 glcUAs in space-filling form (CPK) 6 Hyaluronate solutions viscous, gel–like, compression-resistant occurrence: EC matrix, esp. in developing tissue healing wounds synovial fluid functions: lubricant shock absorber flexible cement attachment site path for cell migration made by fibroblasts degraded by hyaluronidase hyaluronidase bacterial hyaluronidase facilitates spread of infection 7 Alberts et al. Fig. 19-37 Heparin mol wt ~ 104 ~ 40 monosaccharide units made & released from mast cells in lungs & liver heparin cell 8 Heparin mol wt ~ 104 ~ 40 monosaccharide units made & released from mast cells in lungs & liver also associated with luminal surface of endothelium anticoagulant heparin forms complex with antithrombin III this complex binds to thrombin, inactivating it as a result, clot growth is limited fast-acting, making it therapeutically useful 8 cell Extracellular Macromolecules macromolecule % carb. glycosaminoglycans* (GAGs) proteoglycans* 90-95 glycoproteins 2-30 fibrous proteins 1-2 100 Examples of functions: mechanical supportlubrication cushioning adhesives cell spacers selective filters * aka mucopolysaccharides, mucoproteins, respectively Proteoglycans (PGs) composed of as many as 200 GAG chains covalently bonded to a core protein via serine side chains 5 7 molecular weight range: 10 – 10 GAG chains: chondroitin sulfate, heparan sulfate, dermatan sulfate, keratan sulfate Examples decorin many connective tissues binds type I collagen, TGF-β perlecan basal laminae structural & filtering function aggrecan syndecan (slide 13) GAG chains core protein 9 PG in basal lamina of renal glomerulus adapted from Alberts et al., 3 ed., Fig. 19-56 network of fibrous proteins & perlecan PG forms filter entactin perlecan laminin 10 type IV collagen Proteoglycans: aggrecan ~100 GAG chains/molecule ~100 monosaccharides/GAG chain each "bristle" = 1 GAG chain each GAG chain is either chondroitin sulfate or keratan sulfate GAG chains linked to ser side chains of core protein core protein 11 GAG chains An aggregate of aggrecans & hyaluronan major GAG–PG in cartilage link proteins bind noncovalently with bound H2O, disperses shocks, compressive force ~ cell size adhesion proteins link to collagen & hyalurcells onan degraded by chondroitin sulfatase, keratan etc sulfate 12 ç 1μm è core protein link proteins chondroitin sulfate Alberts et al. Fig. 19-41 Proteoglycans: syndecan cell-surface PG core protein domains intracellular transmembrane extracellular 5 GAGs attached GAG chains outside functions interactions cell-cell cell-matrix growth factor receptor 13 inside core protein Lehninger et al. Fig. 9-22 GAG synthesis & breakdown –UDP synthesis activated precursors: UDP–monosaccharide derivatives e.g., UDP–glucuronate residues added one at a time in Golgi complex sulfate moieties donor: PAPS (active sulfate) degradation – – adenine lysosomes – specific glycosidases & sulfatases – mucopolysaccharidoses genetic disorders accumulation of GAG due to absence of a specific glycosidase or sulfatase 14 Extracellular Macromolecules macromolecule % carb. glycosaminoglycans (GAGs) proteoglycans 90-95 glycoproteins* 2-30 fibrous proteins 1-2 100 * polypeptide with 1 or more oligosaccharide side chains 15 Glycoproteins: functions of glyco moieties increase protein’s solubility & hydrophilicity (sl 19) stabilize protein against denaturation proteolysis markers direct protein's destination Glycosylation: one kind of post-translational modification others: phosphorylation carboxylation organelle plasma membrane export (secretion) indicate protein's lifetime (sl 21) part of the protein's receptor recognition site (sl 23) signal factors such as hormones, cytokines cell-cell adhesion proteins 16 Glycoprotein structure polypeptide with 1 or more oligosaccharide side chains oligosaccharide linked to polypeptide in two ways: type linked to side chain of organelle where sugars are added to protein O-linked serine (ser), threonine (thr), Golgi complex lumen (O-glycoside) hydroxylysine (in collagen) N-linked asparagine (asn) rough ER lumen (N-glycoside) 17 Glyco moiety structure oligosaccharide chain extends away from protein surface units mostly hexoses in pyranose (6-atom ring) form branched glycosidic links varied: α or β 1,2; 1,3; 1,4 terminal sugar often sialate 2 asn 7 2 7 asn 18 Stryer 4ed., p. 463 Mucins: salivary glycoproteins mol wt ~ 106 ~800 short (disaccharide) side chains terminal sugar is sialate anionic sugar at end of glyco chains of many glycoproteins very hydrophilic, extended structure 19 ~ ~ galNAc sialate – 2 Mucins: modification & aggregation sialidase (neuraminidase) catalyzes hydrolysis of sialates from mucins secreted by oral bacteria products: less hydrophilic, less H2O-soluble, more folded, more aggregated part of the enamel pellicle & dental plaque matrix 20 ~ ~ x H2O sialidase x ~ ~ ~ ~ galNAc sialate Role of glyco moiety in controlling protein lifetime many blood proteins have glyco chains with terminal sialate endothelial surface sialidases slowly remove sialates from these circulating proteins rate of sialate removal depends on protein's structure sialoglycoprotein: sugars]–protein now-exposed gal–glcNAc… sia–gal–glcNAc–[core residues bind to asialoglycoprotein receptor on liver cell surface asialoglycoprotein: gal–glcNAc–[core sugars]–protein protein is then endocytosed & broken down 21 Blood group types core sugars Type O cell surface: gal–glcNAc–gal–glc–protein† Type A cell surface: galNAc–gal–glcNAc–gal–glc–protein† | fucose* | fucose Type B cell surface: gal–gal–glcNAc–gal–glc–protein† | fucose A: have – enzyme to add galNAc to core sugars – antibody to type B antigen B: have – enzyme to add gal to core sugars – antibody to type A antigen O: have – neither enzyme antibodies AB: have – both enzymes (eitherboth galNAc or gal added to core sugars) 22 † neither antibody or lipid * 6-deoxygalactose Glyco moiety-binding proteins: lectins contain sites that bind specific glyco structures e.g., asialoglycoprotein receptor described on sl 21 important in intercell adhesion (i.e., lectins are CAMs: cell adhesion molecules) selectins: plasma membrane lectins that mediate cell-cell recognition & adhesion 23 Lehninger et al. Fig. 7-37