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Publication Abstract from PubMed

Lasso peptides are a family of ribosomally synthesized and post-translationally modified peptide (RiPP) defined by their threaded-ring topology. The N-terminus of the peptide forms an isopeptide bond with an aspartate or glutamate sidechain to create a 7- to 9-aa macrocyclic ring, through which the rest of the peptide is threaded. The result is a highly constrained 3D structure. Even though they share a threaded-ring feature, characterized lasso peptides vary greatly in sequence and size, ranging from 14 to 26 aa. Using genome mining, we identified a new lasso peptide gene cluster with a predicted lasso peptide that is 33 aa long. Here we report the heterologous expression of this new peptide, pandonodin, its NMR structure, and its unusual biophysical properties. Pandonodin has a long, proteolytically resistant 18-residue tail of low sequence complexity, which limits its water solubility. Within this tail is a 6 aa disulfide-bonded macrocycle that serves as a steric lock to maintain the lasso structure. This disulfide bond is unusually stable, requiring both heat and high concentrations of reductants for cleavage. Finally, we also show that segments of the C-terminal tail of pandonodin can be replaced with arbitrary sequences, allowing for the construction of pandonodin-protein fusions.

Pandonodin: a proteobacterial lasso peptide with an exceptionally long C-terminal tail.,Cheung-Lee WL, Cao L, Link AJ ACS Chem Biol. 2019 Nov 19. doi: 10.1021/acschembio.9b00676. PMID:31742991^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.