6n9e
From Proteopedia
Crystal structure of the Thermus thermophilus 70S ribosome in complex with a short substrate mimic CC-Pmn and bound to mRNA and P-site tRNA at 3.7A resolution
Structural highlights
FunctionRL4_THET8 One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome (By similarity).[HAMAP-Rule:MF_01328_B] Forms part of the polypeptide exit tunnel (By similarity).[HAMAP-Rule:MF_01328_B] This protein can be incorporated into E.coli ribosomes in vivo, which resulted in decreased peptidyltransferase (Ptase) activity of the hybrid ribosomes. The hybrid 50S subunits associate less well with 30S subunits to form the ribosome.[HAMAP-Rule:MF_01328_B] Publication Abstract from PubMedDuring protein synthesis, ribosomes discriminate chirality of amino acids and prevent incorporation of D-amino acids into nascent proteins by slowing down the rate of peptide bond formation. Despite this phenomenon being known for nearly forty years, no structures have ever been reported that would explain the poor reactivity of D-amino acids. Here we report a 3.7A-resolution crystal structure of a bacterial ribosome in complex with a D-aminoacyl-tRNA analog bound to the A site. Although at this resolution we could not observe individual chemical groups, we could unambiguously define the positions of the D-amino acid side chain and the amino group based on chemical restraints. The structure reveals that similarly to L-amino acids, the D-amino acid binds the ribosome by inserting its side chain into the ribosomal A-site cleft. This binding mode does not allow optimal nucleophilic attack of the peptidyl-tRNA by the reactive alpha-amino group of a D-amino acid. Also, our structure suggests that the D-amino acid cannot participate in hydrogen-bonding with the P-site tRNA that is required for the efficient proton transfer during peptide bond formation. Overall, our work provides the first mechanistic insight into the ancient mechanism that helps living cells ensure the stereochemistry of protein synthesis. Mechanistic insights into the slow peptide bond formation with D-amino acids in the ribosomal active site.,Melnikov SV, Khabibullina NF, Mairhofer E, Vargas-Rodriguez O, Reynolds NM, Micura R, Soll D, Polikanov YS Nucleic Acids Res. 2018 Dec 6. pii: 5231803. doi: 10.1093/nar/gky1211. PMID:30520988[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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