No abstract

Cyclic ADP ribose (cADPR) isomers are signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via 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 leading to an active assembly that resembles those of Toll-like receptor adaptor TIR domains. Mutagenesis reveals a conserved tryptophan essential for cyclization. We show that 3′cADPR is an activator of ThsA effector proteins from bacterial anti-phage defense systems termed Thoeris, and a suppressor of plant immunity when produced by the effector HopAM1. Collectively, our results reveal the molecular basis of cADPR isomer production and establish 3′cADPR in bacteria as an antiviral and plant immunity-suppressing signaling molecule.

No abstract

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

LL-37, also called cathelicidin, is an important part of the human immune system, which can resist various pathogens. A plethora of experiments have demonstrated that it has the multifunctional effects of immune regulation, in addition to antimicrobial activity. Recently, there have been increasing interest in its immune function. It was found that LL-37 can have two distinct functions in different tissues and different microenvironments. Thus, it is necessary to investigate LL-37 immune functions from the two sides of the same coin. On the one side, LL-37 promotes inflammation and immune response and exerts its anti-infective and antitumor effects; on the other side, it has the ability to inhibit inflammation and promote carcinogenesis. This review presents a brief summary of its expression, structure, and immunomodulatory effects as well as brief discussions on the role of this small peptide as a key factor in the development and treatment of various inflammation-related diseases and cancers.