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The Significance of Hypervariability and Conserved Motifs in Antimicrobial Peptides from Tree Frogs

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Author(s):
Brunetti, Andres E. ; Fuzo, Carlos A. ; Aguilar, Silvana ; Rivera-Correa, Mauricio ; Marani, Mariela M. ; Lopes, Norberto P.
Total Authors: 6
Document type: Journal article
Source: Journal of Natural Products; v. 86, n. 7, p. 9-pg., 2023-05-23.
Abstract

Amphibians' skin is a richsource of natural antimicrobialpeptides (AMPs). These AMPs exhibit marked inter- and intraspecificsequence divergence linked to the arms race between host and pathogens.Here, we combine peptidomics, molecular modeling, and phylogeneticanalyses to understand the evolution of AMPs in Cophomantini, a diverseclade of neotropical tree frogs, and to investigate their interactionwith bacterial membranes. Consistent with results in other amphibians,all species of Cophomantini secrete a mixture of peptides. We selectedthe hylin peptide family to survey sequence variability and the presenceof common amino acid motifs. We found that most species secrete aunique set of hylins that, though variable, share the conserved motifGly-X-X-X-Pro-Ala-X-X-Gly, with Gly and Pro colocalizing with chargedor polar residues. Our modeling revealed that Pro curves the peptidethrough a hinge, facilitating its insertion into the bacterial membraneand, once inserted, contributes to stabilizing the pore structure.The phylogenetic inference using hylid prepro-peptides showed theneed to classify new AMPs using the full-length sequence of the prepro-peptideregion and highlighted the complex relationships between peptide families.Our findings revealed that conserved motifs occurred independentlyin distinct AMP families, suggesting a convergent evolution and asignificant role in peptide-membrane interactions. (AU)

FAPESP's process: 17/23725-1 - Genomic Analysis of Skin Symbiotic Bacteria in Frogs as Potential Source of Volatile Compounds
Grantee:Andrés Eduardo Brunetti
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 20/02207-5 - Inventorying secondary metabolism applying metabolomic strategies: contribution to the Brazilian biodiversity valuation
Grantee:Norberto Peporine Lopes
Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
FAPESP's process: 14/20915-6 - Chemical ecology in anurans: characterization of volatile compounds and peptide pheromones from the skin secretions of frogs
Grantee:Andrés Eduardo Brunetti
Support Opportunities: Scholarships in Brazil - Post-Doctoral