7X45
Grass carp interferon gamma related
Summary for 7X45
| Entry DOI | 10.2210/pdb7x45/pdb |
| Descriptor | Interferon gamma (2 entities in total) |
| Functional Keywords | cytokine, interferon gamma, interferon gamma related, fish, grass carp |
| Biological source | Ctenopharyngodon idella (grass carp) |
| Total number of polymer chains | 2 |
| Total formula weight | 39295.45 |
| Authors | |
| Primary citation | Zhu, X.,Wang, J.,Jia, Z.,Feng, J.,Wang, B.,Wang, Z.,Liu, Q.,Wu, K.,Huang, W.,Zhao, X.,Dang, H.,Zou, J. Novel Dimeric Architecture of an IFN-gamma-Related Cytokine Provides Insights into Subfunctionalization of Type II IFNs in Teleost Fish. J Immunol., 209:2203-2214, 2022 Cited by PubMed Abstract: Gene duplication leads to subfunctionalization of paralogs. In mammals, IFN-γ is the sole member of the type II IFN family and binds to a receptor complex consisting of IFN-γR1 and IFN-γR2. In teleost fish, IFN-γ and its receptors have been duplicated due to the teleost-specific whole-genome duplication event. In this study, the functions of an IFN-γ-related (IFN-γrel) cytokine were found to be partially retained relative to IFN-γ in grass carp (Ctenopharyngodon idella [CiIFN-γrel]). CiIFN-γrel upregulated the expression of proinflammatory genes but had lost the ability to activate genes involved in Th1 response. The results suggest that CiIFN-γrel could have been subfunctionalized from CiIFN-γ. Moreover, CiIFN-γrel induced STAT1 phosphorylation via interaction with duplicated homologs of IFN-γR1 (cytokine receptor family B [CRFB] 17 and CRFB13). Strikingly, CiIFN-γrel did not bind to the IFN-γR2 homolog (CRFB6). To gain insight into the subfunctionalization, the crystal structure of CiIFN-γrel was solved at 2.26 Å, revealing that it forms a homodimer that is connected by two pairs of disulfide bonds. Due to the spatial positions of helix A, loop AB, and helix B, CiIFN-γrel displays a unique topology that requires elements from two identical monomers to form a unit that is similar to IFN-γ. Further, mutagenesis analyses identified key residues interacting with CiIFN-γrel receptors and those required for the biological functions. Our study can help understand the subfunctionalization of duplicated IFN-γ paralogs in fish. PubMed: 36426983DOI: 10.4049/jimmunol.2200334 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.26 Å) |
Structure validation
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