Resurrecting ancestral structural dynamics of an antiviral immune receptor: adaptive binding pocket reorganization repeatedly shifts RNA preference

BMC Evolutionary Biology

Research Article

Oralia Kolaczkowski¹  Charles Pugh¹  Bryan Korithoski¹  Austin Manny¹  Bryan Kolaczkowski² 

[1] Department of Microbiology & Cell Science and Institute for Food and Agricultural Sciences, University of Florida, Gainesville, USA;Department of Microbiology & Cell Science and Institute for Food and Agricultural Sciences, University of Florida, Gainesville, USA;Genetics Institute, University of Florida, Gainesville, USA;

关键词: RIG-I;    RIG-like receptors;    Ancestral reconstruction;    Antiviral immunity;    Evolution of immunity;    Molecular evolution;    Innate immunity;   

DOI  :  10.1186/s12862-016-0818-6

 received in 2016-10-13, accepted in 2016-10-28,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundAlthough resurrecting ancestral proteins is a powerful tool for understanding the molecular-functional evolution of gene families, nearly all studies have examined proteins functioning in relatively stable biological processes. The extent to which more dynamic systems obey the same ‘rules’ governing stable processes is unclear. Here we present the first detailed investigation of the functional evolution of the RIG-like receptors (RLRs), a family of innate immune receptors that detect viral RNA in the cytoplasm.ResultsUsing kinetic binding assays and molecular dynamics simulations of ancestral proteins, we demonstrate how a small number of adaptive protein-coding changes repeatedly shifted the RNA preference of RLRs throughout animal evolution by reorganizing the shape and electrostatic distribution across the RNA binding pocket, altering the hydrogen bond network between the RLR and its RNA target. In contrast to observations of proteins involved in metabolism and development, we find that RLR-RNA preference ‘flip flopped’ between two functional states, and shifts in RNA preference were not always coupled to gene duplications or speciation events. We demonstrate at least one reversion of RLR-RNA preference from a derived to an ancestral function through a novel structural mechanism, indicating multiple structural implementations of similar functions.ConclusionsOur results suggest a model in which frequent shifts in selection pressures imposed by an evolutionary arms race preclude the long-term functional optimization observed in stable biological systems. As a result, the evolutionary dynamics of immune receptors may be less constrained by structural epistasis and historical contingency.

【 授权许可】

CC BY   
© The Author(s). 2016