7x45

Publication Abstract from PubMed

Gene duplication leads to subfunctionalization of paralogs. In mammals, IFN-gamma is the sole member of the type II IFN family and binds to a receptor complex consisting of IFN-gammaR1 and IFN-gammaR2. In teleost fish, IFN-gamma and its receptors have been duplicated due to the teleost-specific whole-genome duplication event. In this study, the functions of an IFN-gamma-related (IFN-gammarel) cytokine were found to be partially retained relative to IFN-gamma in grass carp (Ctenopharyngodon idella [CiIFN-gammarel]). CiIFN-gammarel upregulated the expression of proinflammatory genes but had lost the ability to activate genes involved in Th1 response. The results suggest that CiIFN-gammarel could have been subfunctionalized from CiIFN-gamma. Moreover, CiIFN-gammarel induced STAT1 phosphorylation via interaction with duplicated homologs of IFN-gammaR1 (cytokine receptor family B [CRFB] 17 and CRFB13). Strikingly, CiIFN-gammarel did not bind to the IFN-gammaR2 homolog (CRFB6). To gain insight into the subfunctionalization, the crystal structure of CiIFN-gammarel was solved at 2.26 A, 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-gammarel displays a unique topology that requires elements from two identical monomers to form a unit that is similar to IFN-gamma. Further, mutagenesis analyses identified key residues interacting with CiIFN-gammarel receptors and those required for the biological functions. Our study can help understand the subfunctionalization of duplicated IFN-gamma paralogs in fish.

Novel Dimeric Architecture of an IFN-gamma-Related Cytokine Provides Insights into Subfunctionalization of Type II IFNs in Teleost Fish.,Zhu X, Wang J, Jia Z, Feng J, Wang B, Wang Z, Liu Q, Wu K, Huang W, Zhao X, Dang H, Zou J J Immunol. 2022 Dec 1;209(11):2203-2214. doi: 10.4049/jimmunol.2200334. PMID:36426983^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.