5hau
From Proteopedia
Crystal structure of antimicrobial peptide Bac7(1-19) bound to the Thermus thermophilus 70S ribosome
Structural highlights
FunctionRL5_THET8 This is 1 of the proteins that binds and probably mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance. In the 70S ribosome it contacts protein S13 of the 30S subunit (forming bridge B1b) connecting the head of the 30S subunit to the top of the 50S subunit. The bridge itself contacts the P site tRNA and is implicated in movement during ribosome translocation. Also contacts the P site tRNA independently of the intersubunit bridge; the 5S rRNA and some of its associated proteins might help stabilize positioning of ribosome-bound tRNAs.[HAMAP-Rule:MF_01333_B] Publication Abstract from PubMedWith bacterial resistance becoming a serious threat to global public health, antimicrobial peptides (AMPs) have become a promising area of focus in antibiotic research. AMPs are derived from a diverse range of species, from prokaryotes to humans, with a mechanism of action that often involves disruption of the bacterial cell membrane. Proline-rich antimicrobial peptides (PrAMPs) are instead actively transported inside the bacterial cell where they bind and inactivate specific targets. Recently, it was reported that some PrAMPs, such as Bac71 -35, oncocins and apidaecins, bind and inactivate the bacterial ribosome. Here we report the crystal structures of Bac71 -35, Pyrrhocoricin, Metalnikowin and two oncocin derivatives, bound to the Thermus thermophilus 70S ribosome. Each of the PrAMPs blocks the peptide exit tunnel of the ribosome by simultaneously occupying three well characterized antibiotic-binding sites and interferes with the initiation step of translation, thereby revealing a common mechanism of action used by these PrAMPs to inactivate protein synthesis. Our study expands the repertoire of PrAMPs and provides a framework for designing new-generation therapeutics. Structures of proline-rich peptides bound to the ribosome reveal a common mechanism of protein synthesis inhibition.,Gagnon MG, Roy RN, Lomakin IB, Florin T, Mankin AS, Steitz TA Nucleic Acids Res. 2016 Mar 18;44(5):2439-50. doi: 10.1093/nar/gkw018. Epub 2016 , Jan 24. PMID:26809677[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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