Presentation on theme: "COLLAGEN CHEMISTRY AND BIOLOGY"— Presentation transcript:
1COLLAGEN CHEMISTRY AND BIOLOGY DEFINITION:A protein with chains containing repetitive Gly-X-Y sequences allowing formation of molecules with triple-helical domains.The triple-helical domains as well as nontriple-helical domains of the molecules interact to form multimolecular aggregates that function primarily as structural elements in extracellular spaces.Collagens are the most abundant protein in mammals (25% of protein mass).
7LOCATIONS OF COLLAGENS (EYE) The lens capsule is a smooth, transparent basement membrane that completely surrounds the lens. The capsule is elastic and is composed of collagen.
8Posterior Polymorphous Corneal Dystrophy One cause is a dominantly actingmutation in a gene encoding forcollagen VIII (COL8A2). Ref: Coupal et al.
9Osteogenesis imperfecta Blue sclerae of an OI victimCaused by genetic mutations in collagen genes COL1A1, COL1A2
10COLLAGEN TYPES 27 types with 45genetically distinct chains: 1.Fiber-forming collagens:the quantitatively predominate collagenschains form several molecular species:(Types I, II, III, V, and XI) + (XXIV and XXVII)procollagen to collagen conversionfibers constructed of staggered, side to side,parallel association of molecules
11COLLAGEN TYPES, CONT.2. Fiber-associated collagens: (IX, XII, XIV, XVI, XIX, XX, XXI, XXII) 3. Network collagens (IV, VIII, X) 4. Filament collagen (VI) 5. Anchoring fibril collagen (VII) 6. Transmembrane collagens: (XIII, XVII, XXIII, XXV) 7. Multiplexins (XV, XVIII) Characteristics: 1) smaller and often numerous helical domains; 2) procollagen to collagen conversion (seldom); 3) staggered, side to side and antiparallel association when aggregates are formed.
12Collagens: primary structure Almost every third residue is glycineApprox 17% is prolineContains hydroxyprolineContains hydroxylysine (which can form interchain bonds or be glycosylated)
13Collagen – A Triple Helix Principal component of connective tissue (tendons, cartilage, bones, teeth)Basic unit is tropocollagen:Three intertwined polypeptide chains (1K residues each)MW = 285,000300 nm long, 1.4 nm diameterUnique amino acid composition, including hydroxylysine and hydroxyprolineHydroxyproline is formed by the vitamin C-dependent prolyl hydroxylase reaction.
15Scurvy (Vitamin C deficiency) Scorbutic gums due to of scurvy. Notice gingival red triangles.Vitamin C is needed for post translational amino acid modifications in collagen.
16Collagen – A Triple Helix The secrets of its a.a. composition...Nearly one residue out of three is GlyProline content is unusually highUnusual amino acids found:4-hydroxyproline3-hydroxyproline5-hydroxylysinePro and HyPro together make 30% of res.
17A case of structure following composition The Collagen Triple HelixA case of structure following compositionThe unusual amino acid composition of collagen is unsuited for alpha helices or beta sheetsIt is ideally suited for the collagen triple helix: three intertwined helical strandsMuch more extended than alpha helix, with a rise per residue of 2.9 Angstroms3.3 residues per turnLong stretches of Gly-Pro-Pro/HyP
18Collagen – A Triple Helix Figure Poly(Gly-Pro-Pro),a collagen-like right-handedtriple helix composed of threeleft-handed helical chains.
19Staggered arrays of tropocollagens Collagen FibersStaggered arrays of tropocollagensBanding pattern in EMs with 68 nm repeatSince tropocollagens are 300 nm long, there must be 40 nm gaps between adjacent tropocollagens (5 x 68 = 340 nm)40 nm gaps are called "hole regions" - they contain carbohydrate and are thought to be nucleation sites for bone formation
20Collagen – A Triple Helix Figure In the electron microscope, collagen fibers exhibit alternating light and dark bands. The dark bands correspond to the 40-nm gaps between pairs of aligned collagen triple helices.
21Pro and HyP suit the constraints of φ and ψ Structural basis of the collagen triple helixEvery third residue faces the crowded center of the helix - only Gly fits herePro and HyP suit the constraints of φ and ψInterchain H-bonds involving HyP stabilize helixFibrils are further strengthened by intrachain lysine-lysine and interchain hydroxypyridinium crosslinks
22The hole regions of collagen fibrils may be the sites of nucleation for bone mineralization A disaccharide of galactose and glucose is covalently linked to the 5-hydroxyl group of hydroxylysines in collagen by the combined action of galactosyltransferase and glucosyltransferase.