Cryo-electron microscopy structures of ArnA, a key enzyme for polymyxin resistance, revealed unexpected oligomerizations and domain movements

Yang, Meng; Chen, Yu Seby; Ichikawa, Muneyoshi; Calles-Garcia, Daniel; Basu, Kaustuv; Fakih, Rayan; Bui, Khanh Huy; Gehring, Kalle

doi:10.1016/j.jsb.2019.07.009

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…E. coli was also highly related to polymyxin resistance gene arnA and mls resistance gene MacA (r = 0Á883, 0Á855). As a crucial enzyme in the lipid A modification pathway, arnA can improve the polymyxin resistance of Gram-negative bacteria (Yang et al 2019). MacA is a peripheral membrane protein.…”

Section: Antibiotic Resistance Genes Alterations In Ibdmentioning

confidence: 99%

Combined analysis of metagenomic data revealed consistent changes of gut microbiome structure and function in inflammatory bowel disease

et al. 2021

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Aims: To reveal the consistency and discrepancy in the gut microbial structure and function in inflammatory bowel disease (IBD) patients from different regions. Methods and Results: Gut microbes, antibiotic resistance genes (ARGs) and virulence factors genes (VFGs) were analysed using metagenome data from three cohorts. The abundance of Escherichia coli extensively increased in IBD patients, whereas Subdoligranulum unclassified decreased dramatically in IBD patients from three countries. Escherichia coli showed a positive correlation with multiple ARGs and VFGs in cohorts from China and the United States, including multidrug-related resistance genes and Capsule and LOS-related virulence factors genes. Escherichia coli biofilm synthesis pathways significantly enriched in IBD patients from three different regions. Notably, Subdoligranulum unclassified and Eubacterium hallii were negatively related to ARGs and VFGs. Conclusions: Consistent changes of microbiome structure and function were observed in IBD patients from three different regions. As pathogenic bacteria, E. coli may accelerate IBD progression through encapsulation in biofilms by upregulating antibiotic resistance in Crohn's disease patients. Subdoligranulum unclassified and E. hallii may be beneficial for IBD patients and could serve as potential probiotics for IBD treatment. Significance and Impact of the Study: This work dispels worries about the regional differences in gut microbial changes in IBD patients and provides useful guidance for more rational microbiome-based therapies.

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Section: Antibiotic Resistance Genes Alterations In Ibdmentioning

confidence: 99%

Combined analysis of metagenomic data revealed consistent changes of gut microbiome structure and function in inflammatory bowel disease

et al. 2021

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“…We have shown in our experiments that our LocSpiral approach improves map connectivity showing fewer fragmented and broken densities and better coverage of the atomic model. In fact, our LocSpiral approach has been applied on several published publications (Ichikawa, Khalifa et al 2019, Yang, Chen et al 2019, Gutmann, Schafer et al 2020, Jahagirdar, Jha et al 2020, Khalifa, Ichikawa et al 2020, enabling molecular modelling on maps with flexibility and light anisotropic resolution.…”

Section: Discussionmentioning

confidence: 99%

Local computational methods to improve the interpretability and analysis of cryo-EM maps

Kaur

Gómez-Blanco

Khalifa

et al. 2020

Preprint

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Cryo-electron microscopy (cryo-EM) maps usually show heterogeneous distributions of B-factors and electron density occupancies and are typically B-factor sharpened to improve their contrast and interpretability at high-resolutions. However, 'over-sharpening' due to the application of a single global B-factor can distort processed maps causing connected densities to appear broken and disconnected. This issue limits the interpretability of cryo-EM maps, i.e. ab initio modelling.In this work, we propose 1) approaches to enhance high-resolution features of cryo-EM maps, while preventing map distortions and 2) methods to obtain local B-factors and electron density occupancy maps. These algorithms have as common link the use of the spiral phase transformation and are called LocSpiral, LocBSharpen, LocBFactor and LocOccupancy. Our results, which

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“…If not stated otherwise, all computational procedures have been performed using the program Relion 3.0.7 (Zivanov et al, 2018). A crystal structure of hexameric ArnA, PDB 4wkg (Fischer et al, 2015;Yang et al, 2019), was fitted in the contamination density (red box). van Zundert et al, 2017).…”

Section: Declaration Of Interestsmentioning

confidence: 99%

Structure and mechanism of a novel cytomegaloviral DCAF mediating interferon antagonism

Le‐Trilling

Banchenko

Paydar

et al. 2022

Preprint

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Human cytomegalovirus (CMV) is a highly relevant pathogen, and its rodent counterparts serve as common infection models. Global proteome profiling of rat CMV-infected cells uncovered a pronounced loss of the transcription factor STAT2, which is crucial for interferon signalling. Deletion mutagenesis documented that STAT2 is targeted by the viral protein E27. Cellular and in vitro analyses showed that E27 exploits host-derived Cullin4-RING ubiquitin ligases (CRL4) to induce poly-ubiquitylation and proteasomal degradation of STAT2. Cryo-electron microscopic structure determination revealed how E27 mimics molecular surface properties of cellular CRL4 substrate receptors (DDB1- and Cullin4-associated factors, DCAFs) to displace them from the CRL4 catalytic core. Moreover, structural analyses elucidated the mechanism of STAT2 recruitment and indicate that E27-binding additionally disturbs STAT2 activation by occupying the IRF9 binding interface. For the first time, these data provide structural insights into cytomegalovirus-encoded interferon antagonism and establish an atomic model for STAT2 counteraction by CRL4 misappropriation with important implications for viral immune evasion.

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Cryo-electron microscopy structures of ArnA, a key enzyme for polymyxin resistance, revealed unexpected oligomerizations and domain movements

Cited by 5 publications

References 42 publications

Combined analysis of metagenomic data revealed consistent changes of gut microbiome structure and function in inflammatory bowel disease

Combined analysis of metagenomic data revealed consistent changes of gut microbiome structure and function in inflammatory bowel disease

Local computational methods to improve the interpretability and analysis of cryo-EM maps

Structure and mechanism of a novel cytomegaloviral DCAF mediating interferon antagonism

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