dc.contributor.author | Zhang, Bing | |
dc.contributor.author | Liu, Caini | |
dc.contributor.author | Qian, Wen | |
dc.contributor.author | Han, Yue | |
dc.contributor.author | Li, Xiaoxia | |
dc.contributor.author | Deng, Junpeng | |
dc.date.accessioned | 2018-08-15T12:44:23Z | |
dc.date.available | 2018-08-15T12:44:23Z | |
dc.date.issued | 2014 | |
dc.identifier | oksd_zhang_structureoftheu_2014 | |
dc.identifier.citation | Zhang, B., Liu, C., Qian, W., Han, Y., Li, X., & Deng, J. (2014). Structure of the unique SEFIR domain from human interleukin 17 receptor A reveals a composite ligand-binding site containing a conserved a-helix for Act1 binding and IL-17 signaling. Acta Crystallographica Section D - Biological Crystallography, 70(5), 1476-1483. https://doi.org/10.1107/S1399004714005227 | |
dc.identifier.uri | https://hdl.handle.net/11244/301417 | |
dc.description.abstract | Interleukin 17 (IL-17) cytokines play a crucial role in mediating inflammatory and autoimmune diseases. A unique intracellular signaling domain termed SEFIR is found within all IL-17 receptors (IL-17Rs) as well as the key adaptor protein Act1. SEFIR-mediated protein–protein interaction is a crucial step in IL-17 cytokine signaling. Here, the 2.3 Å resolution crystal structure of the SEFIR domain of IL-17RA, the most commonly shared receptor for IL-17 cytokine signaling, is reported. The structure includes the complete SEFIR domain and an additional α-helical C-terminal extension, which pack tightly together to form a compact unit. Structural comparison between the SEFIR domains of IL-17RA and IL-17RB reveals substantial differences in protein topology and folding. The uniquely long insertion between strand βC and helix αC in IL-17RA SEFIR is mostly well ordered, displaying a helix (αCC′ins) and a flexible loop (CC′). The DD′ loop in the IL-17RA SEFIR structure is much shorter; it rotates nearly 90° with respect to the counterpart in the IL-17RB SEFIR structure and shifts about 12 Å to accommodate the αCC′ins helix without forming any knots. Helix αC was identified as critical for its interaction with Act1 and IL-17-stimulated gene expression. The data suggest that the heterotypic SEFIR–SEFIR association via helix αC is a conserved and signature mechanism specific for IL-17 signaling. The structure also suggests that the downstream motif of IL-17RA SEFIR together with helix αC could provide a composite ligand-binding surface for recruiting Act1 during IL-17 signaling. | |
dc.format | application/pdf | |
dc.language | en_US | |
dc.publisher | International Union of Crystallography | |
dc.rights | This material has been previously published. In the Oklahoma State University Library's institutional repository this version is made available through the open access principles and the terms of agreement/consent between the author(s) and the publisher. The permission policy on the use, reproduction or distribution of the material falls under fair use for educational, scholarship, and research purposes. Contact Digital Resources and Discovery Services at lib-dls@okstate.edu or 405-744-9161 for further information. | |
dc.title | Structure of the unique SEFIR domain from human interleukin 17 receptor A reveals a composite ligand-binding site containing a conserved a-helix for Act1 binding and IL-17 signaling | |
osu.filename | oksd_zhang_structureoftheu_2014.pdf | |
dc.description.peerreview | Peer reviewed | |
dc.identifier.doi | 10.1107/S1399004714005227 | |
dc.description.department | Biochemistry and Molecular Biology | |
dc.type.genre | Article | |
dc.type.material | Text | |
dc.subject.keywords | act1 binding | |
dc.subject.keywords | il-17 signaling | |
dc.subject.keywords | sefir domain | |
dc.subject.keywords | interleukin 17 receptor a | |