Functions and interplay of the tRNA-binding sites of the ribosome

The ribosome translates the genetic information of an mRNA molecule into a sequence of amino acids. The ribosome utilizes tRNAs to connect elements of the RNA and protein worlds during protein synthesis, i.e. an anticodon as a unit of genetic information with the corresponding amino acid as a building unit of proteins. Three tRNA-binding sites are located on the ribosome, termed the A, P and E sites. In recent years the tRNA-binding sites have been localized on the ribosome by three different techniques, small-angle neutron scattering, cryo-electron microscopy and X-ray analyses of 70 S crystals. These high-resolution glimpses into various ribosomal states together with a large body of biochemical data reveal an intricate interplay between the tRNAs and the three ribosomal binding sites, providing an explanation for the remarkable features of the ribosome, such as the ability to select the correct ternary complex aminoacyl-tRNA · EF-Tu · GTP out of more than 40 extremely similar tRNA complexes, the precise movement of the tRNA2 · mRNA complex during translocation and the maintenance of the reading frame.

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The X-ray structure of the ternary complex GAPDH/NAD/G3P enlightens the role of two anion binding sites during the catalysis

Acta Crystallographica Section A Foundations of Crystallography ◽

10.1107/s0108767300025599 ◽

2000 ◽

Vol 56 (s1) ◽

pp. s261-s261

Author(s):

M. Fatih ◽

C. Didierjean ◽

C. Corbier ◽

S. Boschi-Muller ◽

G. Branlant ◽

...

Keyword(s):

Binding Sites ◽

Ternary Complex ◽

Anion Binding ◽

X Ray

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Structures of new crystal forms ofMycobacterium tuberculosispeptidyl-tRNA hydrolase and functionally important plasticity of the molecule

Acta Crystallographica Section F Structural Biology and Crystallization Communications ◽

10.1107/s1744309111052341 ◽

2012 ◽

Vol 68 (2) ◽

pp. 124-128 ◽

Cited By ~ 3

Author(s):

M. Selvaraj ◽

Rais Ahmad ◽

Umesh Varshney ◽

M. Vijayan

Keyword(s):

Binding Site ◽

Binding Sites ◽

Peptide Binding ◽

Protein Molecule ◽

Solution Nmr ◽

Crystal Forms ◽

X Ray ◽

Peptide Binding Site ◽

Different Sources ◽

Trna Binding

The X-ray structures of new crystal forms of peptidyl-tRNA hydrolase fromM. tuberculosisreported here and the results of previous X-ray studies of the enzyme from different sources provide a picture of the functionally relevant plasticity of the protein molecule. The new X-ray results confirm the connection deduced previously between the closure of the lid at the peptide-binding site and the opening of the gate that separates the peptide-binding and tRNA-binding sites. The plasticity of the molecule indicated by X-ray structures is in general agreement with that deduced from the available solution NMR results. The correlation between the lid and the gate movements is not, however, observed in the NMR structure.

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Probing the druggability of protein–protein interactions: targeting the Notch1 receptor ankyrin domain using a fragment-based approach

Biochemical Society Transactions ◽

10.1042/bst0391327 ◽

2011 ◽

Vol 39 (5) ◽

pp. 1327-1333 ◽

Cited By ~ 12

Author(s):

Noha Abdel-Rahman ◽

Alfonso Martinez-Arias ◽

Tom L. Blundell

Keyword(s):

Crystal Structure ◽

Protein Interactions ◽

Binding Sites ◽

Ternary Complex ◽

Protein Protein Interactions ◽

X Ray ◽

Regulatory Systems ◽

Protein Interfaces ◽

Druggable Genome ◽

Notch1 Receptor

In order to achieve greater selectivity in drug discovery, researchers in both academia and industry are targeting cell regulatory systems. This often involves targeting the protein–protein interactions of regulatory multiprotein assemblies. Protein–protein interfaces are widely recognized to be challenging targets as they tend to be large and relatively flat, and therefore usually do not have the concave binding sites that characterize the so-called ‘druggable genome’. One such prototypic multiprotein target is the Notch transcription complex, where an extensive network of protein–protein interactions stabilize the ternary complex comprising the ankyrin domain, CSL (CBF1/suppressor of Hairless/Lag-1) and MAML (Mastermind-like). Enhanced Notch activity is implicated in the development of T-ALL (T-cell acute lymphoblastic leukaemia) and selective inhibitors of Notch would be useful cancer medicines. In the present paper, we describe a fragment-based approach to explore the druggability of the ankyrin domain. Using biophysical methods and X-ray crystal structure analyses, we demonstrate that molecules can bind to the surface of the ankyrin domain at the interface region with CSL and MAML. We show that they probably represent starting points for designing larger compounds that can inhibit important protein–protein interactions that stabilize the Notch complex. Given the relatively featureless topography of the ankyrin domain, this unexpected development should encourage others to explore the druggability of such challenging multiprotein systems using fragment-based approaches.

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Does a Ribosome Really Read? On the Cognitive Roots and Heuristic Value of Linguistic Metaphors in Molecular Genetics. Part 2

Russian Journal of Philosophical Sciences ◽

10.30727/0235-1188-2020-63-2-46-62 ◽

2020 ◽

Vol 63 (2) ◽

pp. 46-62

Author(s):

Suren T. Zolyan

Keyword(s):

Information Processing ◽

Genetic Information ◽

Formal Organization ◽

Dual Nature ◽

Reading Frame ◽

The Core ◽

Genetic Information Processing ◽

Cognitive Frame ◽

Effective Instrument

We discuss the role of linguistic metaphors as a cognitive frame for the understanding of genetic information processing. The essential similarity between language and genetic information processing has been recognized since the very beginning, and many prominent scholars have noted the possibility of considering genes and genomes as texts or languages. Most of the core terms in molecular biology are based on linguistic metaphors. The processing of genetic information is understood as some operations on text – writing, reading and editing and their specification (encoding/decoding, proofreading, transcription, translation, reading frame). The concept of gene reading can be traced from the archaic idea of the equation of Life and Nature with the Book. Thus, the genetics itself can be metaphorically represented as some operations on text (deciphering, understanding, code-breaking, transcribing, editing, etc.), which are performed by scientists. At the same time linguistic metaphors portrayed gene entities also as having the ability of reading. In the case of such “bio-reading” some essential features similar to the processes of human reading can be revealed: this is an ability to identify the biochemical sequences based on their function in an abstract system and distinguish between type and its contextual tokens of the same type. Metaphors seem to be an effective instrument for representation, as they make possible a two-dimensional description: biochemical by its experimental empirical results and textual based on the cognitive models of comprehension. In addition to their heuristic value, linguistic metaphors are based on the essential characteristics of genetic information derived from its dual nature: biochemical by its substance, textual (or quasi-textual) by its formal organization. It can be concluded that linguistic metaphors denoting biochemical objects and processes seem to be a method of description and explanation of these heterogeneous properties.

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Structures of Rhodopseudomonas palustris RC-LH1 complexes with open or closed quinone channels

Science Advances ◽

10.1126/sciadv.abe2631 ◽

2021 ◽

Vol 7 (3) ◽

pp. eabe2631

Author(s):

David J. K. Swainsbury ◽

Pu Qian ◽

Philip J. Jackson ◽

Kaitlyn M. Faries ◽

Dariusz M. Niedzwiedzki ◽

...

Keyword(s):

Binding Sites ◽

Rhodopseudomonas Palustris ◽

Ring Closure ◽

Light Harvesting Complex ◽

The Core ◽

Quinone Binding ◽

Cryo Electron Microscopy ◽

Unique Protein ◽

Center Light ◽

Resolution Structure

The reaction-center light-harvesting complex 1 (RC-LH1) is the core photosynthetic component in purple phototrophic bacteria. We present two cryo–electron microscopy structures of RC-LH1 complexes from Rhodopseudomonas palustris. A 2.65-Å resolution structure of the RC-LH114-W complex consists of an open 14-subunit LH1 ring surrounding the RC interrupted by protein-W, whereas the complex without protein-W at 2.80-Å resolution comprises an RC completely encircled by a closed, 16-subunit LH1 ring. Comparison of these structures provides insights into quinone dynamics within RC-LH1 complexes, including a previously unidentified conformational change upon quinone binding at the RC QB site, and the locations of accessory quinone binding sites that aid their delivery to the RC. The structurally unique protein-W prevents LH1 ring closure, creating a channel for accelerated quinone/quinol exchange.

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High-resolution cryo-EM structure of photosystem II reveals damage from high-dose electron beams

Communications Biology ◽

10.1038/s42003-021-01919-3 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Koji Kato ◽

Naoyuki Miyazaki ◽

Tasuku Hamaguchi ◽

Yoshiki Nakajima ◽

Fusamichi Akita ◽

...

Keyword(s):

Photosystem Ii ◽

Physiological State ◽

High Dose ◽

Final State ◽

X Ray ◽

Redox States ◽

X Ray Crystallography ◽

Cryo Electron Microscopy ◽

Redox Active ◽

Beam Damage

AbstractPhotosystem II (PSII) plays a key role in water-splitting and oxygen evolution. X-ray crystallography has revealed its atomic structure and some intermediate structures. However, these structures are in the crystalline state and its final state structure has not been solved. Here we analyzed the structure of PSII in solution at 1.95 Å resolution by single-particle cryo-electron microscopy (cryo-EM). The structure obtained is similar to the crystal structure, but a PsbY subunit was visible in the cryo-EM structure, indicating that it represents its physiological state more closely. Electron beam damage was observed at a high-dose in the regions that were easily affected by redox states, and reducing the beam dosage by reducing frames from 50 to 2 yielded a similar resolution but reduced the damage remarkably. This study will serve as a good indicator for determining damage-free cryo-EM structures of not only PSII but also all biological samples, especially redox-active metalloproteins.

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