TIR domain-associated nucleotides with functions in plant immunity and beyond.

TIR (Toll/interlukin-1 receptor) domains are found in archaea, bacteria and eukaryotes, featured in proteins generally associated with immune functions. In plants, they are found in a large group of NLRs (nucleotide-binding leucine-rich repeat receptors), NLR-like proteins and TIR-only proteins. They are also present in effector proteins from phytopathogenic bacteria that are associated with suppression of host immunity.

Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling.

Cyclic adenosine diphosphate (ADP)-ribose (cADPR) isomers are signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via nicotinamide adenine dinucleotide (oxidized form) (NAD) hydrolysis. We show that v-cADPR (2'cADPR) and v2-cADPR (3'cADPR) isomers are cyclized by O-glycosidic bond formation between the ribose moieties in ADPR. Structures of 2'cADPR-producing TIR domains reveal conformational changes that lead to an active assembly that resembles those of Toll-like receptor adaptor TIR domains.

The Impact of Chromate on Molybdenum Homeostasis.

Acquisition of the trace-element molybdenum the high-affinity ATP-binding cassette permease ModABC is essential for respiration in anaerobic and microaerophilic environments. This study determined the X-ray crystal structures of the molybdenum-recruiting solute-binding protein ModA from PAO1 in the metal-free state and bound to the group 6 metal oxyanions molybdate, tungstate, and chromate. PAO1 ModA has a non-contiguous dual-hinged bilobal structure with a single metal-binding site positioned between the two domains.

Structural basis of NLR activation and innate immune signalling in plants.

Animals and plants have NLRs (nucleotide-binding leucine-rich repeat receptors) that recognize the presence of pathogens and initiate innate immune responses. In plants, there are three types of NLRs distinguished by their N-terminal domain: the CC (coiled-coil) domain NLRs, the TIR (Toll/interleukin-1 receptor) domain NLRs and the RPW8 (resistance to powdery mildew 8)-like coiled-coil domain NLRs. CC-NLRs (CNLs) and TIR-NLRs (TNLs) generally act as sensors of effectors secreted by pathogens, while RPW8-NLRs (RNLs) signal downstream of many sensor NLRs and are called helper NLRs.

Structural Evolution of TIR-Domain Signalosomes.

TIR (Toll/interleukin-1 receptor/resistance protein) domains are cytoplasmic domains widely found in animals and plants, where they are essential components of the innate immune system. A key feature of TIR-domain function in signaling is weak and transient self-association and association with other TIR domains. An additional new role of TIR domains as catalytic enzymes has been established with the recent discovery of NAD-nucleosidase activity by several TIR domains, mostly involved in cell-death pathways.

Structural features of Cryptococcus neoformans bifunctional GAR/AIR synthetase may present novel antifungal drug targets.

Cryptococcus neoformans is a fungus that causes life-threatening systemic mycoses. During infection of the human host, this pathogen experiences a major change in the availability of purines; the fungus can scavenge the abundant purines in its environmental niche of pigeon excrement, but must employ de novo biosynthesis in the purine-poor human CNS. Eleven sequential enzymatic steps are required to form the first purine base, IMP, an intermediate in the formation of ATP and GTP.