Location of the Intermolecular Crosslinking Sites in Collagen

  • Norma P. Stimler
  • Marvin L. Tanzer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 86)


Collagen is stabilized by intermolecular crosslinks which occur following the enzymatic conversion of the ε-amino groups of selected lysyl and hydroxylysyl residues to the aldehydes, allysine and hydroxyallysine. These aldehydes combine specifically with other allysine or hydroxyallysine residues and/or the side chains of lysine, hydroxylysine or histidine to produce characteristic crosslinks composed of two, three, or four amino acid components. These crosslinks may be converted to more complex compounds by reaction with other amino acids. The newly discovered crosslink, hydroxyaldol-histidine, appears to arise by condensation of one residue each of allysine, hydroxyallysine, and histidine. It was found in a peptide from a tryptic digest of insoluble calf skin collagen which contains three constituent chains, one arising from a region of αl-CB5 and one from αl-CB6. Data obtained in this laboratory, from peptides which were originally isolated from an extensive proteolytic digest of reconstituted calf skin collagen are consistent with a crosslink between the hydroxylysine at residue 927 in αl-CB6 and the allysine at residue 9N in αl-CB(0,1). This is supported by other investigators who have isolated an analogous crosslinked peptide from CNBr digests. The amino acid sequence of a peptide derived from limited alkaline hydrolysis of insoluble calf bone collagen indicates the presence of the crosslink S,ô’-dihydroxylysinonorleucine at residue 671 in αl-CB7. It is apparent, on both theoretical and experimental bases, that many more cross-linked peptides occur; detailed studies should elucidatethe three-dimensional structure of the collagen fibril.


Collagen Fibril Osteogenesis Imperfecta Bone Collagen Lysyl Oxidase Cyanogen Bromide 
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Copyright information

© Springer Science+Business Media New York 1977

Authors and Affiliations

  • Norma P. Stimler
    • 1
  • Marvin L. Tanzer
    • 1
  1. 1.Department of BiochemistryUniversity of Connecticut Health CenterFarmingtonUSA

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