CSB327 Lecture 10 Summary

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Cell and Systems Biology
Maurice Ringuette

Lecture 10 Decorin - Structure o CS/DS binding domain (N-terminal) o Disulfide loop with C-C disulfide bridge  Collagen binding site  Inhibitory effect on collagen fibrillogenesis o 10 leucine-rich repeats (LRR)  High-affinity collagen binding site o Disulfide loop with C-C disulfide bridge (C-terminal) - Role in collagen fibril formation o A single collagen triple helix at the C-terminus fits in the arch-shaped structure of decorin o The LRRs are high affinity collagen binding sites o Decorin-WT  Collagen fibrils are uniform in size and regularly spaced o Decorin-null  Collagen fibrils are different sizes and unevenly spaced  Similar to EDS o Decorin controls the rate of collagen fibrillogenesis by H-bonding  Core protein regulates the size of the collagen fibrils  CS-GAGs regulates the spacing of collagen fibrils - Role in TGF-β signaling o TGF-β signaling (fibrosis  excessive ECM deposition)  Increased TGF-β promotes fibrosis  Matrix remodelling is deregulated  Characterized by increased ECM components (FN, collagens, SPARC, OPN, etc.) o Decorin binds and inhibits TGF-β signaling  The core protein binds to TGF-β  Injected anti-thymocyte into mice  Decorin treatment o Less fibrosis  No decorin treatment o Fibrosis in kidney leads to renal failure - Role in atherogenesis o DS form is present in arteries, skin and lungs o CS form is present in cartilage  High affinity for LDL o In arteries, DS form changes to CS form  Cause lipoprotein plaques in the blood Biglycan - Structure o CS/DS binding domain (N-terminal) o Disulfide loop with C-C disulfide bridge o 10 leucine-rich repeats o Disulfide loop with C-C disulfide bridge (C-terminal) - Osteopenia o Low bone mineral density - Osteoporosis o Low bone mass o Loss of bone tissue o Leading to increased fragile bones o Leading to increased risk of fractures - Osteogenesis o Osteoid is non-mine
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