CSB327 Lecture 3 Summary

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Cell and Systems Biology
Maurice Ringuette

CSB327 Lecture 3 Notes - Covalent cross-link formation (collagen molecule  collagen fibril) o Aldol cross-links between two modified lysine side chains  Intramolecular cross-links occurs within the triple heli  Intermolecular cross-links occur between the N-terminal and C-terminal telopeptide domains o Aldol cross-links are catalyzed by an extracellular enzyme called lysyl oxidase (LO)  Lys and HO-Lys residues are deaminated by lysyl oxidase  Creates highly reactive aldehyde derivatives  Spontaneously forms aldol cross-link o Pro-LO is cleaved into LO by BMP1 o Lysine cross-links in adult skin, cornea and sclera o HO-lysine cross links in bone, cartilage, ligament, tendon, embryonic skin, and most major internal connective tissues - Fibrillogenesis (collagen fibril  collagen fiber) o Lateral interactions of adjacent collagen molecules are quarter staggered or displaced by 1 D (65-67 nm) period  1 D is comprised of 0.6 D (hole zone) and 0.4 D (overlap zone)  Function of hole zone o Access to modifying enzymes such as LO o Site of hydroxyapeptite (calcium-phosphate) crystal formation (mineralization) o Fibril flexibility  Creates striation appearance of collagen in EM micrograph  Positive stain o Binds to regions rich in polar amino acids  Negative stain o Trapped in the hole zones o Collagen molecule is 4.4 D therefore, the collagen molecules are quarter staggered because displaced by about ¼ of their length o Collagen fibril half life is about 6 months  Triple helices are resistant to protease, hence turnover is accomplished by MMP o Another form of fibrillar collagen assembly is segment long spacing (SLS)  Isolated from embryonic
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