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

Background: Although 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.

Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication.

The RIG-like receptors (RLRs) are related proteins that identify viral RNA in the cytoplasm and activate cellular immune responses, primarily through direct protein-protein interactions with the signal transducer, IPS1. Although it has been well established that the RLRs, RIG-I and MDA5, activate IPS1 through binding between the twin caspase activation and recruitment domains (CARDs) on the RLR and a homologous CARD on IPS1, it is less clear which specific RLR CARD(s) are required for this interaction, and almost nothing is known about how the RLR-IPS1 interaction evolved. In contrast to what has been observed in the presence of immune-modulating K63-linked polyubiquitin, here we show that-in the absence of ubiquitin-it is the first CARD domain of human RIG-I and MDA5 (CARD1) that binds directly to IPS1 CARD, and not the second (CARD2).

Ancient origins of vertebrate-specific innate antiviral immunity.

Animals deploy various molecular sensors to detect pathogen infections. RIG-like receptor (RLR) proteins identify viral RNAs and initiate innate immune responses. The three human RLRs recognize different types of RNA molecules and protect against different viral pathogens.

The involvement of the pyruvate dehydrogenase E1alpha subunit, in Streptococcus mutans acid tolerance.

Streptococcus mutans, an etiological agent of dental caries, is a normal inhabitant of dental plaque. Two main virulence factors of S. mutans are acidogenicity and aciduricity - the ability to produce acid and survive at low pH, respectively.

Involvement of the detoxifying enzyme lactoylglutathione lyase in Streptococcus mutans aciduricity.

Streptococcus mutans, a normal inhabitant of dental plaque, is considered a primary etiological agent of dental caries. Its main virulence factors are acidogenicity and aciduricity, the abilities to produce acid and to survive and grow at low pH, respectively. Metabolic processes are finely regulated following acid exposure in S.

Transport and metabolism of citrate by Streptococcus mutans.

Streptococcus mutans, a normal inhabitant of dental plaque, is considered a primary etiological agent of dental caries. Two virulence determinants of S. mutans are its acidogenicity and aciduricity (the ability to produce acid and the ability to survive and grow at low pH, respectively).

Tropheryma whippelii as a cause of afebrile culture-negative endocarditis: the evolving spectrum of Whipple's disease.

With the advent of molecular diagnostics culture-negative endocarditis caused by the organism Tropheryma whippelii is an increasingly described entity. We describe two patients with afebrile, culture-negative endocarditis caused by T. whippelii who had neither the gastrointestinal nor arthritic manifestations of Whipple's disease.