Genetic and crystallographic approaches to investigating ribosome structure and function

Gregory, Steven T.; DeMi̇rci̇, Hasan; Carr, Jennifer F.; Belardinelli, Riccardo; Thompson, Jessica; Cameron, Dale M.; Rodriguez-Correa, Daniel; Murphy, F.V.; Jogl, G.; Dahĺberg, Albert E.

doi:10.1007/978-3-7091-0215-2_5

Cited by 2 publications

(3 citation statements)

References 40 publications

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“…A previous site-directed mutagenesis and gene replacement study on the Thermus thermophilus ribosome provided strong evidence of an allosteric communication between DC and EF-Tu linked by S12 and A/T-tRNA (Gregory et al, 2009). The highly conserved QEH triplet of S12 (Gln78, Glu79, His80) was proposed to take a role in transmitting the codon recognition signal to EF-Tu (Gregory et al, 2011). Moreover, the antibiotic dityromycin binds the exact region predicted by our hub residue analysis, as demonstrated by structural studies on Escherichia coli (Bulkley et al, 2014).…”

Section: Residues With High Betweenness Scores Link Small and Large Subunits Of The Bacterial Ribosomementioning

confidence: 99%

“…Moreover, mutation studies suggested that bridges B5, B6, and B8 are important parts of a network of interactions affecting decoding fidelity by changing the GTPase activity of EF-Tu (Sun et al, 2011). There is also evidence for the role of tRNAs in allosteric communication in the ribosome structure (Schmeing et al, 2009;Sethi et al, 2009;Gregory et al, 2011).…”

Section: Residues With High Betweenness Scores Link Small and Large Subunits Of The Bacterial Ribosomementioning

confidence: 99%

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Exploring allosteric communication in multiple states of the bacterial ribosome using residue network analysis

Kürkçüoğlu¹

2018

Turk J Biol

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Antibiotic resistance is one of the most important problems of our era and hence the discovery of new effective therapeutics is urgent. At this point, studying the allosteric communication pathways in the bacterial ribosome and revealing allosteric sites/residues is critical for designing new inhibitors or repurposing readily approved drugs for this enormous machine. To shed light onto molecular details of the allosteric mechanisms, here we construct residue networks of the bacterial ribosomal complex at four different states of translation by using an effective description of the intermolecular interactions. Centrality analysis of these networks highlights the functional roles of structural components and critical residues on the ribosomal complex. High betweenness scores reveal pathways of residues connecting numerous sites on the structure. Interestingly, these pathways assemble highly conserved residues, drug binding sites, and known allosterically linked regions on the same structure. This study proposes a new residue-level model to test how distant sites on the molecular machine may be linked through hub residues that are critically located on the contact topology to inherently form communication pathways. Findings also indicate intersubunit bridges B1b, B3, B5, B7, and B8 as critical targets to design novel antibiotics.

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Section: Residues With High Betweenness Scores Link Small and Large Subunits Of The Bacterial Ribosomementioning

confidence: 99%

Section: Residues With High Betweenness Scores Link Small and Large Subunits Of The Bacterial Ribosomementioning

confidence: 99%

Exploring allosteric communication in multiple states of the bacterial ribosome using residue network analysis

Kürkçüoğlu¹

2018

Turk J Biol

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“…RAMTases methylate an intermediate of the rSSU and are necessary for its maturation (Connolly et al 2008; Desai and Rife 2006; Lafontaine et al 1998; O’Farrell et al 2006). They may also help to optimize mature rSSUs for protein synthesis (Connolly et al 2008; Gregory et al 2011). In addition to the presence of RAMTases within the three domains of life, proteins of this family were likely also encoded in the genomes of the endosymbiotic progenitors of plastids and mitochondria (Lisowsky and Michaelis 1988; Patron et al 2005; Rife 2009; Shutt and Gray 2006).…”

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confidence: 99%

Phylogenetic Reconstruction Shows Independent Evolutionary Origins of Mitochondrial Transcription Factors from an Ancient Family of RNA Methyltransferase Proteins

Harris

Goldman

2018

J Mol Evol

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Here, we generate a robust phylogenetic framework for the rRNA adenine N(6)-methyltransferase (RAMTase) protein family that shows a more ancient and complex evolutionary history within the family than previously reported. RAMTases occur universally by descent across the three domains of life, and typical orthologs within the family perform methylation of the small subunits of ribosomal RNA (rRNA). However, within the RAMTase family, two different groups of mitochondrial transcription factors, mtTFB1 and mtTFB2, have evolved in eukaryotes through neofunctionalization. Previous phylogenetic analyses have suggested that mtTFB1 and mtTFB2 comprise sister clades that arose via gene duplication, which occurred sometime following the endosymbiosis event that produced the mitochondrion. Through dense and taxonomically broad sampling of RAMTase family members especially within bacteria, we found that these eukaryotic mitochondrial transcription factors, mtTFB1 and mtTFB2, have independent origins in phylogenetically distant clades such that their divergence most likely predates the last universal common ancestor of life. The clade of mtTFB2s comprises orthologs in Opisthokonts and the clade of mtTFB1s includes orthologs in Amoebozoa and Metazoa. Thus, we clearly demonstrate that the neofunctionalization producing the transcription factor function evolved twice independently within the RAMTase family. These results are consistent with and help to elucidate outcomes from prior experimental studies, which found that some members of mtTFB1 still perform the ancestral rRNA methylation function, and the results have broader implications for understanding the evolution of new protein functions. Our phylogenetic reconstruction is also in agreement with prior studies showing two independent origins of plastid RAMTases in Viridiplantae and other photosynthetic autotrophs. We believe that this updated phylogeny of RAMTases should provide a robust evolutionary framework for ongoing studies to identify and characterize the functions of these proteins within diverse organisms.Electronic supplementary materialThe online version of this article (10.1007/s00239-018-9842-z) contains supplementary material, which is available to authorized users

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Genetic and crystallographic approaches to investigating ribosome structure and function

Cited by 2 publications

References 40 publications

Exploring allosteric communication in multiple states of the bacterial ribosome using residue network analysis

Exploring allosteric communication in multiple states of the bacterial ribosome using residue network analysis

Phylogenetic Reconstruction Shows Independent Evolutionary Origins of Mitochondrial Transcription Factors from an Ancient Family of RNA Methyltransferase Proteins

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