Although the mode of action of the ribosomes, the multi-component universal effective protein-synthesis organelles, has been thoroughly explored, their mere appearance remained elusive. Our earlier comparative structural studies suggested that a universal internal small RNA pocket-like segment called by us the protoribosome, which is still embedded in the contemporary ribosome, is a vestige of the primordial ribosome. Herein, after constructing such pockets, we show using the "fragment reaction" and its analyses by MALDI-TOF and LC–MS mass spectrometry techniques, that several protoribosome constructs are indeed capable of mediating peptide-bond formation. These findings present strong evidence supporting our hypothesis on origin of life and on ribosome's construction, thus suggesting that the protoribosome may be the missing link between the RNA dominated world and the contemporary nucleic acids/proteins life.
A semi-symmetric vestige of an RNA apparatus with stereochemically controlled ribozyme capabilities is embedded and functions as the site of peptide bond formation within all contemporary ribosomes, a finding that is in line with Lahav and Leiserowitz earlier discoveries on stereochemically controlled chemical reactions. As the structure of this semi-symmetrical self-folded RNA entity is almost fully conserved in all known ribosomes, it seems to be resilient to evolution, thus hinting at its pre-biotic origin and hence, suggested by us, to be the protoribosome. Recent studies, described shortly below, demonstrated peptide bond formation by the laboratory-designed protoribosomes, which supports the notion that a pre-biotic bonding entity is still functioning in all contemporary ribosomes.
Giardiasis is a disease caused by the protist Giardia lamblia. As no human vaccines have been approved so far against it, and resistance to current drugs is spreading, new strategies for combating giardiasis need to be developed. The G. lamblia ribosome may provide a promising therapeutic target due to its distinct sequence differences from ribosomes of most eukaryotes and prokaryotes. Here, we report the cryo-electron microscopy structure of the G. lamblia (WB strain) ribosome determined at 2.75 Å resolution. The ribosomal RNA is the shortest known among eukaryotes, and lacks nearly all the eukaryote-specific ribosomal RNA expansion segments. In contrast, the ribosomal proteins are typically eukaryotic with some species-specific insertions/extensions. Most typical inter-subunit bridges are maintained except for one missing contact site. Unique structural features are located mainly at the ribosome’s periphery. These may be exploited as target sites for the design of new compounds that inhibit selectively the parasite’s ribosomal activity.
The mechanism that regulates the translocation step in ribosomes during protein synthesis is not fully understood. In this work, cryo-EM techniques used to image ribosomes from
Staphylococcus aureus
after incubation at physiological temperature allowed the identification of a conformation of the helix 68 that has never been observed so far.
(S,S)- and (R,R)-β,γ-Bis-substituted PNAs were synthesized from the C-2 symmetric vicinal diamine system embedded in 1,4 dihydroxybutane and 1,4-dimethoxybutane scaffolds. (R,R)-β,γ-Bis-methoxymethyl-PNA derived from d-tartaric acid was found to be in the right configuration and conformation to be an excellent mimic of PNA, endowed with superior ability to enter into cells.
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