《糖生物学》课程教学课件（讲稿）12 proteoglycans and glycolipids

2.5 Proteoglycans(蛋白聚糖）are heavilyO-glycosylated proteins that givestrength to the extracellular matrix

2.5 Proteoglycans(蛋白聚糖) are heavily O-glycosylated proteins that give strength to the extracellular matrix

.Proteoglycans bind water, but they providestructure rather than lubrication. O-linked glycans of a mucin is small: Glycans attached to proteoglycans are verylarge, containing as many as 100 residues. Linear chains consisting of alternating aminosugars and hexopyranosides: Names of glycosaminoglycans (GAG) reflectthe tissue originally isolated

• Proteoglycans-bind-water,-but-they-provide￾structure-rather-than-lubrica7on- • O9linked-glycans-of-a-mucin-is-small- • Glycans-a>ached-to-proteoglycans-are-very￾large,-containing-as-many-as-100-residues- • Linear-chains-consis7ng-of-alterna7ng-amino￾sugars-and-hexopyranosides • Names-of-glycosaminoglycans-(GAG)-reflect￾the-7ssue-originally-isolated-

AunitBunitProteincoreLinkageTissuesGlycosaminoglycanNoGlcAGIcNAcNoneConnectivetissues,skinHyaluronic acidcartilagesynovialfluid透明质酸GlcAGalNAcYesO-XyloseChondroitin sulphateCartilage, cornea, bone,skin,arteries硫酸软骨素YesO-XyloseDermatan sulphateGlcA/ldoAGalNAcSkin,bloodvesselsheartvalves硫酸皮肤素GlcNAcYesO-XyloseGlcA/ldoALung,arteries,Heparan sulphatecellsurfaces硫酸乙酰肝素GalYesN-GIcNAcCartilage,corneaKeratan sulphateGlcNAc硫酸角质HHCOOHHLOHOHOHOOHOHHOHOGalβ1-3Galβ1-4Xyl1-SerHCOO-OHOHGlyHHHHO-Xylose linkage regionD-Glucuronic acidL-lduronic acid(GlcA)(ldoA)Hyalin(透明素）membrane,cartilage（软骨),and skin

透明质酸
硫酸软骨素
硫酸皮肤素
硫酸乙酰肝素
硫酸角质
Hyalin-(透明素)-membrane,-car7lage-(软骨),-and-skin

.Two major classes: those found in extracellularmatrixandthoselocatedinplasmamembranes. Those found in structure tissues are bestunderstood:e.g.cartilage(软骨)。Thecollagen（胶原蛋白)fibresofcartilageprovidestiffness (resistance to bending) and strength(resistance to pulling)·Proteoglycans provide resilience(弹性),resistantto compression(压缩)underpressure This function depends on a high degree ofsupramolecularorganization

• Two-major-classes:-those-found-in-extracellular￾matrix-and-those-located-in-plasma-membranes- • Those-found-in-structure-7ssues-are-best￾understood:-e.g.-car7lage-(软骨)- • The-collagen-(胶原蛋白)-fibres-of-car7lage-provide￾s7ffness-(resistance-to-bending)-and-strength- (resistance-to-pulling)- • Proteoglycans-provide-resilience(弹性),-resistant￾to-compression-(压缩)-under-pressure- • This-func7on-depends-on-a-high-degree-of￾supramolecular-organiza7on-

CollagennmOnly glyProeasyOnlyglyOnlvalychempolymerproject.wikispaces.com

chempolymerproject.wikispaces.com Collagen(

AggregateMonomerMw:2.5x108(expandedbelow)100-200M上手XHLLaggrecanMw:2.5x106-EpidermalgrowthMonomerfactor-likeHyaluronicdomainacido名名名名OO名名名名名O名0000O0名名OO名O-OOO量O量OOOOOOdComplementrepeatOOG2+名名名G300OO名名O名名名COo名名名名古名名名LinkooOOOOmodulesC-type lectin-G1likedomainLink+proteinGlcNAcGlcAOGalChondroitinKeratanGalNAcIdoAOMansulphatesulphateSer-Gly-xylose30/50100/100

Mw：2.5×106- 100/100 30/50 1009200 Mw：2.5×108- aggrecan Ser,Gly,xylose(

. Providing resilience incartilage is a consequenceof their highly hydrated state.Waterbinding is mediated by the sugars andlarge amount of sulphate residues· Resulting large volume occupied by anaggregate. It can only be reduced under pressure, byreleasing water· Aggregates are molecular shock absorbers orverystiffsponges· Releasing waterslowly under pressureandtaking it back up when pressure is released

• Providing-resilience-in-car7lage-is-a-consequence￾of-their-highly-hydrated-state- • Water-binding-is-mediated-by-the-sugars-and￾large-amount-of-sulphate-residues- • Resul7ng-large-volume-occupied-by-an￾aggregate- • It-can-only-be-reduced-under-pressure,-by￾releasing-water- • Aggregates-are-molecular-shock-absorbers-or￾very-s7ff-sponges- • Releasing-water-slowly-under-pressure-and￾taking-it-back-up-when-pressure-is-released-

Cartilage in various joints （关节）and invertebraldiscs（椎盘）effectivelycushions（缓冲）thejolts（震动）GAG-attachment regions becomelongerSegments of the aggrecan gene encoding thisportionareexpanded

Segments-of-the-aggrecan-gene-encoding-this￾por7on-are-expanded Cartilage in various joints (关节) and in vertebral discs (椎盘) effectively cushions (缓 冲) the jolts (震动) ! GAG-attachment regions become longer!

o In fowls (鸡)oNaturallyoccurringnanomelia（短肢畸形mutation(突变) results in a truncatedaggrecan core protein lacking much of theGAG and C-terminal G3 globular domaino The mutant protein fails to support normallong-bone development, resulting in drasticskeletal（骨骼）abnormalities（异常）

o In-fowls-(鸡)- o Naturally-occurring-nanomelia-(短肢畸形)- muta7on-(突变)-results-in-a-truncated￾aggrecan-core-protein-lacking-much-of-the￾GAG-and-C9terminal-G3-globular-domain￾o The-mutant-protein-fails-to-support-normal￾long9bone-development,-resul7ng-in-dras7c￾skeletal-(骨骼)-abnormali7es-(异常)-

o Proteoglycans found in extracellular matrices oftissueotherthancartilageo Core proteins of neurocan in brain and versican inblood vessels, skin, and other tissues closelyresembleaggrecanoDifferentGAGcanbeconjugatedo E.g. Perlican, a complex modular protein consistingof multiple copies of at least six different types ofglobulardomainand bearing just afewGAG chainso No details of selections of GAG providing physicaland organizational properties that suit therequirementofindividualtissues

o Proteoglycans-found-in-extracellular-matrices-of- 7ssue-other-than-car7lage￾o Core-proteins-of-neurocan in-brain-and-versican in￾blood-vessels,-skin,-and-other-7ssues-closely￾resemble-aggrecan o Different-GAG-can-be-conjugated￾o E.g.-Perlican,-a-complex-modular-protein-consis7ng￾of-mul7ple-copies-of-at-least-six-different-types-of￾globular-domain-and-bearing-just-a-few-GAG-chains- o No-details-of-selec7ons-of-GAG-providing-physical￾and-organiza7onal-proper7es-that-suit-the￾requirement-of-individual-7ssues-