5V1V

TbiB1 in Complex with the TbiA(alpha) Leader Peptide

Summary for 5V1V

• Entry DOI: 10.2210/pdb5v1v/pdb
• Related: 5V1U
• Descriptor: TbiB1, TbiA(alpha) Leader Peptide, ZINC ION, ... (4 entities in total)
• Functional Keywords: lasso peptide, ripp, peptide binding, protein binding
• Biological source: Thermobaculum terrenum (strain ATCC BAA-798 / YNP1); More
• Total number of polymer chains: 4
• Total formula weight: 25631.27

Authors

Chekan, J.R.,Nair, S.K. (deposition date: 2017-03-02, release date: 2018-09-05, Last modification date: 2024-03-06)

Primary citation

Chekan, J.R.,Ongpipattanakul, C.,Nair, S.K.
Steric complementarity directs sequence promiscuous leader binding in RiPP biosynthesis.
Proc.Natl.Acad.Sci.USA, 116:24049-24055, 2019

PubMed Abstract: Enzymes that generate ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products have garnered significant interest, given their ability to produce large libraries of chemically diverse scaffolds. Such RiPP biosynthetic enzymes are predicted to bind their corresponding peptide substrates through sequence-specific recognition of the leader sequence, which is removed after the installation of posttranslational modifications on the core sequence. The conservation of the leader sequence within a given RiPP class, in otherwise disparate precursor peptides, further supports the notion that strict sequence specificity is necessary for leader peptide engagement. Here, we demonstrate that leader binding by a biosynthetic enzyme in the lasso peptide class of RiPPs is directed by a minimal number of hydrophobic interactions. Biochemical and structural data illustrate how a single leader-binding domain can engage sequence-divergent leader peptides using a conserved motif that facilitates hydrophobic packing. The presence of this simple motif in noncognate peptides results in low micromolar affinity binding by binding domains from several different lasso biosynthetic systems. We also demonstrate that these observations likely extend to other RiPP biosynthetic classes. The portability of the binding motif opens avenues for the engineering of semisynthetic hybrid RiPP products.

PubMed: 31719203
DOI: 10.1073/pnas.1908364116

Experimental method

X-RAY DIFFRACTION (1.35 Å)