Details

Autor(en) / Beteiligte

• Wu, Bingyuan
• Muzammil, Salman
• Jones, Brian
• Nemeth, Jennifer F.
• Janecki, Dariusz J.
• Baker, Audrey
• Merle Elloso, M.
• Naso, Michael
• Carton, Jill
• Taudte, Susann

Titel

The role of interchain disulfide bond in a recombinant human interleukin-17A variant

Ist Teil von

• Cytokine (Philadelphia, Pa.), 2014-02, Vol.65 (2), p.167-174

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• •Refolding of a human interleukin-17A (IL-17A) variant results in covalent and non-covalent dimers.•The interchain disulfide is not essential for IL-17A dimerization.•The interchain disulfide plays a great role in IL-17’s thermostability and biological activity. Interleukin-17A (IL-17A) is the prototype of IL-17 family and has been implicated in the pathogenesis of a variety of autoimmune diseases. Therefore its structural and functional properties are of great medical interest. During our research on a recombinant human IL-17A (rhIL-17A) variant, four isoforms were obtained when it was refolded. While isoforms 1 and 2 represented non-covalent dimers, isoforms 3 and 4 were determined to be covalent dimers. All four isoforms were structurally similar by Circular Dichroism and fluorescence spectroscopy studies, but differential scanning calorimetry demonstrated thermal stability in the order of isoform 1=isoform 2<isoform 4<isoform 3. In addition, compared to covalent dimers (isoform 3 and 4), the non-covalent dimers (isoforms 1 and 2) are slightly less active in a receptor-binding assay but at least 5-fold less active in a cell-based assay.