bims-tricox Biomed News
on Translation, ribosomes and COX
Issue of 2023–07–09
seven papers selected by
Yash Verma, University of Zurich
  1. Principles of human pre-60S biogenesis.
  2. Regulation of electron transfer in the terminal step of the respiratory chain.
  3. Membrane insertases at a glance.
  4. Ribosomal proteins can hold a more accurate record of bacterial thermal adaptation compared to rRNA.
  5. ChatGPT, GPT-4, and other large language models - the next revolution for clinical microbiology?
  6. To eat or not to eat mitochondria? How do host cells cope with mitophagy upon bacterial infection?
  7. Cryo2Struct : A Large Labeled Cryo-EM Density Map Dataset for AI-based Reconstruction of Protein Structures.
  1. Science. 2023 Jul 07. 381(6653): eadh3892
    Principles of human pre-60S biogenesis.
    Arnaud Vanden Broeck, Sebastian Klinge.
      During the early stages of human large ribosomal subunit (60S) biogenesis, an ensemble of assembly factors establishes and fine-tunes the essential RNA functional centers of pre-60S particles by an unknown mechanism. Here, we report a series of cryo-electron microscopy structures of human nucleolar and nuclear pre-60S assembly intermediates at resolutions of 2.5 to 3.2 angstroms. These structures show how protein interaction hubs tether assembly factor complexes to nucleolar particles and how guanosine triphosphatases and adenosine triphosphatase couple irreversible nucleotide hydrolysis steps to the installation of functional centers. Nuclear stages highlight how a conserved RNA-processing complex, the rixosome, couples large-scale RNA conformational changes with pre-ribosomal RNA processing by the RNA degradation machinery. Our ensemble of human pre-60S particles provides a rich foundation with which to elucidate the molecular principles of ribosome formation.
    DOI:  https://doi.org/10.1126/science.adh3892
  2. Biochem Soc Trans. 2023 Jul 06. pii: BST20221449. [Epub ahead of print]
    Regulation of electron transfer in the terminal step of the respiratory chain.
    Wataru Sato, Koichiro Ishimori.
      In mitochondria, electrons are transferred along a series of enzymes and electron carriers that are referred to as the respiratory chain, leading to the synthesis of cellular ATP. The series of the interprotein electron transfer (ET) reactions is terminated by the reduction in molecular oxygen at Complex IV, cytochrome c oxidase (CcO) that is coupled with the proton pumping from the matrix to the inner membrane space. Unlike the ET reactions from Complex I to Complex III, the ET reaction to CcO, mediated by cytochrome c (Cyt c), is quite specific in that it is irreversible with suppressed electron leakage, which characterizes the ET reactions in the respiratory chain and is thought to play a key role in the regulation of mitochondrial respiration. In this review, we summarize the recent findings regarding the molecular mechanism of the ET reaction from Cyt c to CcO in terms of specific interaction between two proteins, a molecular breakwater, and the effects of the conformational fluctuation on the ET reaction, conformational gating. Both of these are essential factors, not only in the ET reaction from Cyt c to CcO, but also in the interprotein ET reactions in general. We also discuss the significance of a supercomplex in the terminal ET reaction, which provides information on the regulatory factors of the ET reactions that are specific to the mitochondrial respiratory chain.
    Keywords:  breakwater; complex IV; conformational gating; cytochrome c; electron transfer; supercomplex
    DOI:  https://doi.org/10.1042/BST20221449
  3. J Cell Sci. 2023 Jul 01. pii: jcs261219. [Epub ahead of print]136(13):
    Membrane insertases at a glance.
    Büsra Kizmaz, Johannes M Herrmann.
      Protein translocases, such as the bacterial SecY complex, the Sec61 complex of the endoplasmic reticulum (ER) and the mitochondrial translocases, facilitate the transport of proteins across membranes. In addition, they catalyze the insertion of integral membrane proteins into the lipid bilayer. Several membrane insertases cooperate with these translocases, thereby promoting the topogenesis, folding and assembly of membrane proteins. Oxa1 and BamA family members serve as core components in the two major classes of membrane insertases. They facilitate the integration of proteins with α-helical transmembrane domains and of β-barrel proteins into lipid bilayers, respectively. Members of the Oxa1 family were initially found in the internal membranes of bacteria, mitochondria and chloroplasts. Recent studies, however, also identified several Oxa1-type insertases in the ER, where they serve as catalytically active core subunits in the ER membrane protein complex (EMC), the guided entry of tail-anchored (GET) and the GET- and EMC-like (GEL) complex. The outer membrane of bacteria, mitochondria and chloroplasts contain β-barrel proteins, which are inserted by members of the BamA family. In this Cell Science at a Glance article and the accompanying poster, we provide an overview of these different types of membrane insertases and discuss their function.
    Keywords:  BAM complex; EMC complex; GET complex; Membrane insertases; Oxa1; Protein biogenesis; Translocases; YidC; β-barrel proteins
    DOI:  https://doi.org/10.1242/jcs.261219
  4. Nucleic Acids Res. 2023 Jul 03. pii: gkad560. [Epub ahead of print]
    Ribosomal proteins can hold a more accurate record of bacterial thermal adaptation compared to rRNA.
    Antonia van den Elzen, Karla Helena-Bueno, Charlotte R Brown, Lewis I Chan, Sergey V Melnikov.
      Ribosomal genes are widely used as 'molecular clocks' to infer evolutionary relationships between species. However, their utility as 'molecular thermometers' for estimating optimal growth temperature of microorganisms remains uncertain. Previously, some estimations were made using the nucleotide composition of ribosomal RNA (rRNA), but the universal application of this approach was hindered by numerous outliers. In this study, we aimed to address this problem by identifying additional indicators of thermal adaptation within the sequences of ribosomal proteins. By comparing sequences from 2021 bacteria with known optimal growth temperature, we identified novel indicators among the metal-binding residues of ribosomal proteins. We found that these residues serve as conserved adaptive features for bacteria thriving above 40°C, but not at lower temperatures. Furthermore, the presence of these metal-binding residues exhibited a stronger correlation with the optimal growth temperature of bacteria compared to the commonly used correlation with the 16S rRNA GC content. And an even more accurate correlation was observed between the optimal growth temperature and the YVIWREL amino acid content within ribosomal proteins. Overall, our work suggests that ribosomal proteins contain a more accurate record of bacterial thermal adaptation compared to rRNA. This finding may simplify the analysis of unculturable and extinct species.
    DOI:  https://doi.org/10.1093/nar/gkad560
  5. Clin Infect Dis. 2023 Jul 03. pii: ciad407. [Epub ahead of print]
    ChatGPT, GPT-4, and other large language models - the next revolution for clinical microbiology?
    Adrian Egli.
      ChatGPT, GPT-4, and Bard are highly advanced natural language process (NLP)-based computer programmes (chatbots) that simulate and process human conversation in written or spoken form. Recently released by the company OpenAI, ChatGPT was trained on billions of unknown text elements (tokens) and rapidly gained wide attention for its ability to respond to questions in an articulate manner across a wide range of knowledge domains. These potentially disruptive large language model (LLM) technologies have a broad range of conceivable applications in medicine and medical microbiology. In this opinion article, I will describe how chatbot technologies work and discuss the strength and weaknesses of ChatGPT, GPT-4, and other LLMs for applications in the routine diagnostic laboratory, focussing on various use cases for the pre- to post-analytical process.
    Keywords:  ChatGPT; GPT-4; Large language models; artificial intelligence; chatbot; digitalization
    DOI:  https://doi.org/10.1093/cid/ciad407
  6. PLoS Pathog. 2023 Jul;19(7): e1011471
    To eat or not to eat mitochondria? How do host cells cope with mitophagy upon bacterial infection?
    Jérémy Verbeke, Xavier De Bolle, Thierry Arnould.
      Mitochondria fulfil a plethora of cellular functions ranging from energy production to regulation of inflammation and cell death control. The fundamental role of mitochondria makes them a target of choice for invading pathogens, with either an intracellular or extracellular lifestyle. Indeed, the modulation of mitochondrial functions by several bacterial pathogens has been shown to be beneficial for bacterial survival inside their host. However, so far, relatively little is known about the importance of mitochondrial recycling and degradation pathways through mitophagy in the outcome (success or failure) of bacterial infection. On the one hand, mitophagy could be considered as a defensive response triggered by the host upon infection to maintain mitochondrial homeostasis. However, on the other hand, the pathogen itself may initiate the host mitophagy to escape from mitochondrial-mediated inflammation or antibacterial oxidative stress. In this review, we will discuss the diversity of various mechanisms of mitophagy in a general context, as well as what is currently known about the different bacterial pathogens that have developed strategies to manipulate the host mitophagy.
    DOI:  https://doi.org/10.1371/journal.ppat.1011471
  7. bioRxiv. 2023 Jun 15. pii: 2023.06.14.545024. [Epub ahead of print]
    Cryo2Struct : A Large Labeled Cryo-EM Density Map Dataset for AI-based Reconstruction of Protein Structures.
    Nabin Giri, Jianlin Cheng.
      The advent of single-particle cryogenic electron microscopy (cryo-EM) has brought forth a new era of structural biology, enabling the routine determination of large biological protein complexes and assemblies at atomic resolution. The high-resolution structures of protein complexes and assemblies significantly expedite biomedical research and drug discovery. However, automatically and accurately reconstructing protein structures from high-resolution density maps generated by cryo-EM is still time-consuming and challenging when template structures for the protein chains in a target protein complex are unavailable. Artificial intelli-gence (AI) methods such as deep learning trained on limited amounts of labeled cryo-EM density maps generate unstable reconstructions. To address this issue, we created a dataset called Cryo2Struct consisting of 7,600 preprocessed cryo-EM density maps whose voxels are labelled according to their corresponding known protein structures for training and testing AI methods to infer protein structures from density maps. It is larger and has better quality than any existing, publicly available dataset. We trained and tested deep learning models on Cryo2Struct to make sure it is ready for the large-scale development of AI methods for reconstructing protein structures from cryo-EM density maps. The source code, data and instructions to reproduce our results are freely available at https://github.com/BioinfoMachineLearning/cryo2struct .
    DOI:  https://doi.org/10.1101/2023.06.14.545024
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