| First Author | Kramer JM | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 10 | Pages | 6379-83 |
| PubMed ID | 17982023 | Mgi Jnum | J:153875 |
| Mgi Id | MGI:4366432 | Doi | 10.4049/jimmunol.179.10.6379 |
| Citation | Kramer JM, et al. (2007) Cutting edge: identification of a pre-ligand assembly domain (PLAD) and ligand binding site in the IL-17 receptor. J Immunol 179(10):6379-83 |
| abstractText | IL-17 is the hallmark cytokine of the newly described 'Th17' lymphocyte population. The composition, subunit dynamics, and ligand contacts of the IL-17 receptor are poorly defined. We previously demonstrated that the IL-17RA subunit oligomerizes in the membrane without a ligand. In this study, computational modeling identified two fibronectin-III-like (FN) domains in IL-17RA connected by a nonstructured linker, which we predicted to mediate homotypic interactions. In yeast two-hybrid, the membrane-proximal FN domain (FN2), but not the membrane-distal domain (FN1), formed homomeric interactions. The ability of FN2 to drive ligand-independent multimerization was verified by coimmunoprecipitation and fluorescence resonance energy transfer microscopy. Thus, FN2 constitutes a 'pre-ligand assembly domain' (PLAD). Further studies indicated that the FN2 linker domain contains the IL-17 binding site, which was never mapped. However, the FN1 domain is also required for high affinity interactions with IL-17. Therefore, although the PLAD is located entirely within FN2, effective ligand binding also involves contributions from the linker and FN1. |
