Proline-rich antimicrobial peptides (PrAMPs) internalize into susceptible bacteria using specific transporters and interfere with protein synthesis and folding. To date, mammalian PrAMPs have so far only been identified in artiodactyls. Since cetaceans are co-phyletic with artiodactyls, we mined the genome of the bottlenose dolphin Tursiops truncates, leading to the identification of two PrAMPs, Tur1A and Tur1B. Tur1A, which is orthologous to the bovine PrAMP Bac7, is internalized into E. coli without damaging the membranes using the inner membrane transporters SbmA and YjiL/MdM. Furthermore, like Bac7, Tur1A also inhibits bacterial protein synthesis by binding to the ribosome and blocking the transition from the initiation to the elongation phase. By contrast, Tur1B is a poor inhibitor of protein synthesis and appears to act predominantly via disrupting bacterial membranes. An X-ray structure of Tur1A bound within the ribosomal exit tunnel provides a basis to develop these peptides as novel antimicrobial agents.

The Dolphin Proline-Rich Antimicrobial Peptide Tur1A Inhibits Protein Synthesis by Targeting the Bacterial Ribosome

Mardirossian, Mario
Methodology
;
Benincasa, Monica
Methodology
;
Gambato, Stefano
Methodology
;
Tossi, Alessandro
Supervision
;
2018

Abstract

Proline-rich antimicrobial peptides (PrAMPs) internalize into susceptible bacteria using specific transporters and interfere with protein synthesis and folding. To date, mammalian PrAMPs have so far only been identified in artiodactyls. Since cetaceans are co-phyletic with artiodactyls, we mined the genome of the bottlenose dolphin Tursiops truncates, leading to the identification of two PrAMPs, Tur1A and Tur1B. Tur1A, which is orthologous to the bovine PrAMP Bac7, is internalized into E. coli without damaging the membranes using the inner membrane transporters SbmA and YjiL/MdM. Furthermore, like Bac7, Tur1A also inhibits bacterial protein synthesis by binding to the ribosome and blocking the transition from the initiation to the elongation phase. By contrast, Tur1B is a poor inhibitor of protein synthesis and appears to act predominantly via disrupting bacterial membranes. An X-ray structure of Tur1A bound within the ribosomal exit tunnel provides a basis to develop these peptides as novel antimicrobial agents.
22-feb-2018
Epub ahead of print
http://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(18)30044-8
File in questo prodotto:
File Dimensione Formato  
10.1016@j.chembiol.2018.02.004.pdf

non disponibili

Tipologia: Documento in Versione Editoriale
Licenza: Copyright Editore
Dimensione 2.21 MB
Formato Adobe PDF
2.21 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
2921544_10.1016@j.chembiol.2018.02.004-PostPrint.pdf

accesso aperto

Descrizione: Post Print VQR3
Tipologia: Bozza finale post-referaggio (post-print)
Licenza: Digital Rights Management non definito
Dimensione 2.71 MB
Formato Adobe PDF
2.71 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/2921544
Citazioni
  • ???jsp.display-item.citation.pmc??? 29
  • Scopus 50
  • ???jsp.display-item.citation.isi??? 46
social impact