SummaryThe developmentally complex soil microbe Streptomyces tendae secretes a hydrophobic peptide that restored to developmental mutants of S. coelicolor the ability to raise aerial hyphae. The S. tendae peptide, SapT, has a lantibiotic structure and molecular modelling predicts that it is amphiphilic, making it structurally and functionally similar to the SapB peptide produced by S. coelicolor. However, SapT, which bears three β β β β -methyl lanthionine bridges and one lanthionine bridge and demonstrated limited antibiotic activity, is distinct from SapB. The amphiphilic nature of both SapT and SapB is required for their ability to serve as biosurfactants facilitating the emergence of newly formed aerial hyphae. Remarkably, SapB and SapT, and the fungal hydrophobin SC3 were shown to restore to a SapB-deficient S. coelicolor mutant the capacity to undergo complete morphogenesis, such that the extracellular addition of protein resulted in sporulation. This suggests that the initiation of aerial growth may also indirectly trigger the signal transduction events needed for differentiation. These data imply that the production of morphogenetic peptides may be common among the streptomycetes, but that while their ability to function as biosurfactants is conserved, their specific lantibiotic structure is not. Finally, the identification of a second lanthionine-containing morphogenetic peptide suggests that lantibiotic structure and function may be more diverse than previously thought.

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The catalytic domain of protein tyrosine kinases can interconvert between active and inactive conformations in response to regulatory inputs. We recently demonstrated that Src kinase features an allosteric network that couples substrate-binding sites. However, the extent of conformational and dynamic changes that are propagated throughout the kinase domain remains poorly understood. Here, we monitor by NMR the effect of conformationally selective inhibitors on kinase backbone dynamics. We find that inhibitor binding and activation loop autophosphorylation induces dynamic changes across the entire kinase. We identify a highly conserved amino acid, Gly449, that is necessary for Src activation. Finally, we show for the first time how the SH3–SH2 domains perturb the dynamics of the kinase domain in the context of the full length protein. We provide experimental support for long-range communication in Src kinase that leads to the relative stabilization of active or inactive conformations and modulation of substrate affinity.