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Publication Abstract from PubMed

Interferon alpha (IFNalpha) is a type I interferon, an essential cytokine employed by the immune system to fight viruses. Although a number of the structures of type I interferons have been reported, most of the known structures of IFNalpha are in complex with its receptors. There are only two examples of structures of free IFNalpha: one is a dimeric X-ray structure without side-chain information; and another is an NMR structure of human IFNalpha. Although we have shown that Sortilin is involved in the secretion of IFNalpha, the details of the molecular interaction and the secretion mechanism remain unclear. Recently, we solved the X-ray structure of mouse Sortilin, but the structure of mouse IFNalpha remained unknown. In the present study, we determined the crystal structure of mouse IFNalpha2 at 2.1 A resolution and investigated its interaction with Sortilin. Docking simulations suggested that Arg22 of mouse IFNalpha2 is important for the interaction with mouse Sortilin. Mutation of Arg22 to alanine facilitated IFNalpha2 secretion, as determined by flow cytometry, highlighting the contribution of this residue to the interaction with Sortilin. These results suggest an important role for Arg22 in mouse IFNalpha for Sortilin-mediated IFNalpha trafficking.

Detailed Structure of Mouse Interferon alpha2 and Its Interaction with Sortilin.,Watanabe H, Yabe-Wada T, Onai N, Unno M J Biochem. 2021 Mar 25. pii: 6189106. doi: 10.1093/jb/mvab038. PMID:33769476^[2]

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