Collagen II containing a Cys substitution for arg-alpha1-519. Homotrimeric monomers containing the mutation do not assemble into fibrils but alter the self-assembly of the normal protein. Academic Article uri icon

abstract

  • A recombinant system was used to prepare human type II procollagen containing the substitution of Cys for Arg at alpha1-519 found in three unrelated families with early onset generalized osteoarthritis together with features of a mild chondrodysplasia probably best classified as spondyloepiphyseal dysplasia. In contrast to mutated procollagens containing Cys substitutions for obligatory Gly residues, the Cys substitution at alpha1-519 did not generate any intramolecular disulfide bonds. The results were consistent with computer modeling experiments that demonstrated that the alpha carbon distances were shorter with Cys substitutions for obligatory Gly residues than with Cys substitutions in the Y position residues in repeating -Gly-X-Y- sequences of the collagen triple helix. The mutated collagen did not assemble into fibrils under conditions in which the normal monomers polymerized. However, the presence of the mutated monomer in mixtures with normal collagen II increased the lag time for fibril assembly and altered the morphology of the fibrils formed.

published proceedings

  • J Biol Chem

altmetric score

  • 3

author list (cited authors)

  • Fertala, A., Ala-Kokko, L., Wiaderkiewicz, R., & Prockop, D. J

citation count

  • 29

complete list of authors

  • Fertala, A||Ala-Kokko, L||Wiaderkiewicz, R||Prockop, DJ

publication date

  • March 1997