Proteoglycans

Proteoglycans are macromolecules consisting of a core protein covalently attached to one or more glycosaminoglycan (GAG) chains. They are essential components of the extracellular matrix (ECM) and cell surfaces, where they play key roles in hydration, structure, signaling, and cell communication.

Structure:

  • Core Protein: Provides the backbone for GAG attachment.
  • GAG Chains: Long, negatively charged carbohydrate chains such as:
  • Most proteoglycans have multiple GAG chains, except decorin, which has only one.

🟡 Note: Hyaluronic acid is a GAG, not covalently attached to a core protein, so it forms aggregates with proteoglycans but is not itself a proteoglycan.

Function:

FunctionDescription
Hydration and cushioningGAGs attract water, creating a gel-like ECM that resists compression, especially in cartilage and skin.
Structural supportHelp maintain tissue architecture by filling space and anchoring cells in the ECM.
Cell signalingBind growth factors and cytokines, affecting cell behavior (growth, migration, differentiation).
Barrier and filtrationContribute to selective permeability in tissues like the kidney glomerulus.

Examples of Proteoglycans:

ProteoglycanLocationFunction
AggrecanCartilageMajor load-bearing and hydrating molecule
DecorinConnective tissueRegulates collagen fibril formation
PerlecanBasement membranesSupports filtration and cell signaling
SyndecanCell surfaceInvolved in wound healing and growth factor signaling
VersicanECM of various tissuesInvolved in cell adhesion and tissue development

Proteoglycans vs. Glycoproteins:

FeatureProteoglycansGlycoproteins
Sugar contentHigh (up to 95% of weight is GAGs)Lower (short branched oligosaccharides)
GAG typeLong, repeating, often sulfatedShort, varied sugars
RoleStructural, regulatory, and hydratingEnzymatic, hormonal, or immune functions

Clinical Relevance:

  • Osteoarthritis: Loss of aggrecan and GAGs leads to cartilage breakdown.
  • Cancer: Altered expression of cell-surface proteoglycans like syndecans can affect tumor growth and metastasis.
  • Genetic disorders: Mutations in proteoglycan synthesis pathways cause skeletal and connective tissue diseases (e.g., Ehlers-Danlos syndrome).
  • Therapeutic use: Proteoglycan-derived materials are used in biomaterials and regenerative medicine.

Summary Table:

PropertyDescription
Basic ComponentsCore protein + one or more GAG chains
LocationECM, cartilage, skin, basement membranes, cell surfaces
FunctionsHydration, structural support, signaling, tissue repair
Common ExamplesAggrecan, decorin, perlecan, syndecan, versican
Medical ImportanceArthritis, cancer, tissue engineering