4woi
From Proteopedia
4,5-linked aminoglycoside antibiotics regulate the bacterial ribosome by targeting dynamic conformational processes within intersubunit bridge B2
Structural highlights
FunctionRS5_ECOLI With S4 and S12 plays an important role in translational accuracy. Many suppressors of streptomycin-dependent mutants of protein S12 are found in this protein, some but not all of which decrease translational accuracy (ram, ribosomal ambiguity mutations).[1] Located at the back of the 30S subunit body where it stabilizes the conformation of the head with respect to the body.[2] The physical location of this protein suggests it may also play a role in mRNA unwinding by the ribosome, possibly by forming part of a processivity clamp.[3] Publication Abstract from PubMedDynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit, respectively, impacts translation by controlling intersubunit rotation. Here we show that aminoglycosides chemically related to neomycin-paromomycin, ribostamycin and neamine-each bind to sites within h44 and H69 to perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which only differ by their ring-I 6'-polar group, drive subunit rotation in opposite directions. This suggests that their distinct actions hinge on the 6'-substituent and the drug's net positive charge. By solving the crystal structure of the paromomycin-ribosome complex, we observe specific contacts between the apical tip of H69 and the 6'-hydroxyl on paromomycin from within the drug's canonical h44-binding site. These results indicate that aminoglycoside actions must be framed in the context of bridge B2 and their regulation of subunit rotation. Chemically related 4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions.,Wasserman MR, Pulk A, Zhou Z, Altman RB, Zinder JC, Green KD, Garneau-Tsodikova S, Doudna Cate JH, Blanchard SC Nat Commun. 2015 Jul 30;6:7896. doi: 10.1038/ncomms8896. PMID:26224058[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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