Evidence of Cis/Trans-Isomerization at Pro7/Pro16 in the Lasso Peptide Microcin J25.
Branched-cyclic peptides
Lasso topologies
Site-directed mutagenesis
Trapped ion mobility spectrometry–mass spectrometry
Journal
Journal of the American Society for Mass Spectrometry
ISSN: 1879-1123
Titre abrégé: J Am Soc Mass Spectrom
Pays: United States
ID NLM: 9010412
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
received:
10
12
2018
accepted:
08
01
2019
revised:
08
01
2019
pubmed:
6
3
2019
medline:
6
3
2019
entrez:
6
3
2019
Statut:
ppublish
Résumé
Microcin J25 is a ribosomal synthesized and post-translationally modified peptide (RiPP) characterized by a mechanically interlocked topology called the lasso fold. This structure provides microcin J25 a potent antimicrobial activity resulting from internalization via the siderophore receptor FhuA and further inhibition of the RNA polymerase. In the present work, nuclear magnetic resonance (NMR) and trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) were used to investigate the lasso structure of microcin J25. NMR experiments showed that the lasso peptide microcin J25 can adopt conformational states where Pro16 can be found in the cis- and trans-orientations. The high-resolution mobility analysis, aided by site-directed mutagenesis ([P7A], [P16A], and [P7A/P16A] variants), demonstrated that microcin J25 can adopt cis/cis-, cis/trans-, trans/cis-, and trans/trans-conformations at the Pro7 and Pro16 peptide bonds. It was also shown that interconversion between the conformers can occur as a function of the starting solvent conditions and ion heating (collision-induced activation, CIA) despite the lasso topology. Complementary to NMR findings, the cis-conformations at Pro7 were assigned using TIMS-MS. This study highlights the analytical power of TIMS-MS and site-directed mutagenesis for the study of biological systems with large micro-heterogeneity as a way to further increase our understanding of the receptor-binding dynamics and biological activity.
Identifiants
pubmed: 30834511
doi: 10.1007/s13361-019-02134-5
pii: 10.1007/s13361-019-02134-5
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1038-1045Subventions
Organisme : Directorate for Mathematical and Physical Sciences
ID : CHE-1654274
Organisme : Agence Nationale de la Recherche
ID : BLAN-NT09-692063
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