The role of interchain disulfide bond in a recombinant human interleukin-17A variant |
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| Institution: | 1. Biologics Research, Janssen Research and Development, LLC., 1400 McKean Road, Spring House, PA 19477, United States;2. Immunology Discovery Research, Janssen Research and Development, LLC., 1400 McKean Road, Spring House, PA 19477, United States;1. Louisiana State University Health Sciences Center, Department of Pediatrics, The Research Institute for Children’s Hospital, USA;2. Department of Pulmonary Medicine,1542 Tulane Avenue, New Orleans, LA 70112, USA;3. University of South Alabama College of Medicine, Department of Pediatrics, 2451 Fillingim St., Mobile, AL 36617, USA;1. Xi’an Institute of Optics and Precision Mechanics of Chinese Academy of Sciences, Xi’an 710119, Shaanxi, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;3. From the Departments of Microbiology and;4. Pathology, University of Alabama at Birmingham, and;5. the Birmingham Veterans Affairs Medical Center, Research Department, Birmingham, Alabama 35294;1. Graduate School, Southern Medical University, Guangzhou 510515, China;2. Department of Cardiology, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China;3. Department of Cardiology Hospital, Shanghai 200135, China;4. Department of Ultrasound, Guangzhou Liuhuaqiao Hospital, Guangzhou 510010, China;5. Department of Cardiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China;6. Department of Cardiology, East Hospital, Tongji University, Shanghai 200120, China |
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| Abstract: | 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. |
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| Keywords: | IL-17A Refolding Disulfide bond Activity |
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