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1篇 您的检索式:作者名="David WBurt"
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1Functional divergence of oligoadenylate synthetase 1(OAS1)proteins in Tetrapods显示文摘OASs play critical roles in immune response against virus infection by polymerizing ATP into 2-5 As,which initiate the classical OAS/RNase L pathway and induce degradation of viral RNA.OAS members are functionally diverged in four known innate immune pathways(OAS/RNase L,OASL/IRF7,OASL/RIG-I,and OASL/cGAS),but how they functionally diverged is unclear.Here,we focus on evolutionary patterns and explore the link between evolutionary processes and functional divergence of Tetrapod OAS1.We show that Palaeognathae and Primate OAS1 genes are conserved in genomic and protein structures but differ in function.The former(i.e.,ostrich)efficiently synthesized long 2-5 A and activated RNase L,while the latter(i.e.,human)synthesized short 2-5 A and did not activate RNase L.We predicted and verified that two in-frame indels and one positively selected site in the active site pocket contributed to the functional divergence of Palaeognathae and Primate OAS1.Moreover,we discovered and validated that an in-frame indel in the C-terminus of Palaeognathae OAS1 affected the binding affinity of ds RNA and enzymatic activity,and contributed to the functional divergence of Palaeognathae OAS1 proteins.Our findings unravel the molecular mechanism for functional divergence and give insights into the emergence of novel functions in Tetrapod OAS1.Xiaoxue Wang Jiaxiang Hu Linfei Song Enguang Rong Chenghuai Yang Xiaoyun Chen Juan Pu Honglei Sun Chuze Gao David WBurt Jinhua Liu Ning Li Yinhua Huang 2022Science China(Life Sciences)2022,65,7:1
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