G protein-coupled receptors (GPCRs) represent a large family of signaling proteins that includes many therapeutic targets. GPCR ligands include odorants, tastants, and neurotransmitters and vary in size and properties. Dramatic chemical diversity may occur even among ligands of the same receptor. Our goal is to unravel the structural and chemical features that determine GPCRs' promiscuity towar...

Xenematide, a cyclic depsipeptide antibiotic produced by Xenorhabdus nematophila, had a candidate nonribosomal peptide synthetase (NRPS) with atypical features. Differential metabolite analysis between a mutant and wildtype validated that this stand-alone NRPS was required for xenematide production, and further analysis led to a series of new xenematide derivatives encoded by the same NRPS. Our...

Membrane-associated guanylate kinases (MAGUKs) constitute a family of scaffold molecules involved in diverse cellular processes, such as cell–cell communication, cell polarity, and signal transduction (1). MAGUKs are multidomain proteins with a core structure consisting of PSD-95/DLG/ ZO-1 (PDZ), Src homolgy 3 (SH3), and enzymatically inactive guanylate kinase (GK) domains. Although full-length...

Kin selection theory has been one of the most significant advances in our understanding of social behavior . However, the discovery of widespread promiscuity has challenged the evolutionary importance of kin selection because it reduces the benefit associated with helping nestmates . This challenge would be resolved if promiscuous species evolved a self-referent kin-recognition mechanism that e...