Expression, Purification, and Refolding of Recombinant Collagen α1(Xi) Amino Terminal Domain Splice Variants

Lisa R. Warner, Christina M. Blasick, Raquel J. Brown, Julia Thom Oxford

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The amino terminal domain of collagen type XI α1 chain is a noncollagenous structure that is essential for the regulation of fibrillogenesis in developing cartilage. The amino terminal domain is alternatively spliced at the mRNA level, resulting in proteins expressed as splice variants. These splice variants, or isoforms, have unique distribution in growing tissues, alluding to distinct roles in development. We report here a rapid and straightforward method for expression, purification and in vitro folding of recombinant collagen XI isoforms α1(XI) NTD[p7] and α1(XI) NTD[p6b+7]. The recombinant isoforms were expressed in Escherichia coli as bacterial inclusion bodies. Unfolded carboxy terminal polyhistidine tagged proteins were purified via nickel affinity chromatography and refolded with specific protocols optimized for each isoform. Purity was assessed by SDS–PAGE and correct secondary structure by a comparison of circular dichroism data with that obtained for Npp. Protein expression and purification of the recombinant collagen XI splice variants will allow further studies to elucidate the structure and molecular interactions with components of the extracellular matrix. This research will clarify the mechanism of collagen XI mediated regulation of collagen fibrillogenesis.

Original languageAmerican English
Pages (from-to)403-409
Number of pages7
JournalProtein Expression and Purification
Volume52
Issue number2
DOIs
StatePublished - 1 Apr 2007

Keywords

  • Alternative splicing
  • Amino terminal domain
  • Cartilage
  • Collagen

EGS Disciplines

  • Biology

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