Cited by Structural basis for CaVα2δ-gabapentin binding

EMC chaperone–CaV structure reveals an ion channel assembly intermediate DOI

Zhou Chen, Abhisek Mondal, Fayal Abderemane-Ali

et al.

Nature, Journal Year: 2023, Volume and Issue: 619(7969), P. 410 - 419

Published: May 17, 2023

Language: Английский

Citations

Bacterial sensor evolved by decreasing complexity DOI

Elizabet Monteagudo‐Cascales, J.A. Gavira, Jiawei Xing

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(5)

Published: Jan. 29, 2025

Bacterial receptors feed into multiple signal transduction pathways that regulate a variety of cellular processes including gene expression, second messenger levels, and motility. Receptors are typically activated by binding to ligand-binding domains (LBDs). Cache omnipresent LBDs found in bacteria, archaea, eukaryotes, humans. They form the predominant family extracytosolic bacterial were identified all major receptor types. composed either single (sCache) or double (dCache) structural module. The functional relevance bimodular remains poorly understood. Here, we identify PacF chemoreceptor phytopathogen Pectobacterium atrosepticum recognizes formate at membrane-distal module its dCache domain, triggering chemoattraction. We further demonstrate formate-specific sCache has evolved from exemplified PacF, losing membrane-proximal By solving high-resolution structures two members complex with formate, show molecular basis for is highly similar, despite their low sequence identity. apparent loss may be related observation bind ligands module, whereas studies have failed find bound This work advances our understanding sensing suggests evolution reducing complexity route shaping diversity.

Language: Английский

Citations

MiST 4.0: a new release of the microbial signal transduction database, now with a metagenomic component DOI

Vadim M. Gumerov,

Luke E. Ulrich,

Igor B. Zhulin

et al.

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(D1), P. D647 - D653

Published: Oct. 4, 2023

Abstract Signal transduction systems in bacteria and archaea link environmental stimuli to specific adaptive cellular responses. They control gene expression, motility, biofilm formation, development other processes that are vital survival. The microbial signal (MiST) database is an online resource stores tens of thousands genomes allows users explore their profiles, analyze bulk using the application programming interface (API) make testable hypotheses about functions newly identified signaling systems. However, metagenomes remained completely unexplored. To lay foundation for research metagenomic transduction, we have prepared a new release MiST database, 4.0, which features over 10 000 metagenome-assembled (MAGs), scaled representation proteins detailed BioSample information. In addition, several been processed stored database. A has developed seamlessly switch between MAGs. 4.0 freely available at https://mistdb.com; MAGs can also be explored API on same page.

Language: Английский

Citations

Origin and functional diversification of PAS domain, a ubiquitous intracellular sensor DOI

Jiawei Xing, Vadim M. Gumerov, Igor B. Zhulin

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(35)

Published: Aug. 30, 2023

Signal perception is a key function in regulating biological activities and adapting to changing environments. Per-Arnt-Sim (PAS) domains are ubiquitous sensors found diverse receptors bacteria, archaea, eukaryotes, but their origins, distribution across the tree of life, extent functional diversity not fully characterized. Here, we show that using sequence conservation structural information, it possible propose specific potential functions for large portion nearly 3 million PAS domains. Our analysis suggests originated bacteria were horizontally transferred archaea eukaryotes. We reveal gas sensing via heme cofactor evolved independently several lineages, whereas redox light flavin adenine dinucleotide mononucleotide cofactors have same origin. The close relatedness human those provides an opportunity drug design by exploring natural ligands bacterial homologs.

Language: Английский

Citations

Ubiquitous purine sensor modulates diverse signal transduction pathways in bacteria DOI

Elizabet Monteagudo‐Cascales, Vadim M. Gumerov, Matilde Fernández

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 12, 2024

Abstract Purines and their derivatives control intracellular energy homeostasis nucleotide synthesis, act as signaling molecules. Here, we combine structural sequence information to define a purine-binding motif that is present in sensor domains of thousands bacterial receptors modulate motility, gene expression, metabolism, second-messenger turnover. Microcalorimetric titrations selected validate ability specifically bind purine derivatives, evolutionary analyses indicate sensors share common ancestor with amino-acid receptors. Furthermore, provide experimental evidence physiological relevance sensing system modulates c-di-GMP levels.

Language: Английский

Citations

Specificities of Chemosensory Receptors in the Human Gut Microbiota DOI

Wenhao Xu, Ekaterina Jalomo-Khayrova, Vadim M. Gumerov

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

The human gut is rich in metabolites and harbors a complex microbial community, yet the sensory repertoire of its commensal bacteria remains largely uncharacterized. Here we systematically mapped ligand specificities extracytoplasmic domains from twenty members microbiota, with primary focus on abundant physiologically important class Clostridia. We identified diverse as specific stimuli for three major functional classes transmembrane receptors. further characterized novel subsets sensors belonging to Cache superfamily, lactate, dicarboxylic acids, uracil short-chain fatty acids (SCFAs), respectively, investigated evolution their specificity. Structural biochemical analysis newly described dCache_1UR domain revealed an independent binding SCFA at distinct modules. Altogether, could identify or predict over half Cache-type chemotactic selected commensals, carboxylic representing largest ligands. Among those, most commonly found were lactate formate, indicating particular importance these microbiome consistent observed beneficial impact growth bacterial species.

Language: Английский

Citations

Biallelic CACNA2D1 loss-of-function variants cause early-onset developmental epileptic encephalopathy DOI

Shehrazade Dahimène,

Leonie von Elsner, Tess Holling

et al.

Brain, Journal Year: 2022, Volume and Issue: 145(8), P. 2721 - 2729

Published: Feb. 25, 2022

Voltage-gated calcium (CaV) channels form three subfamilies (CaV1-3). The CaV1 and CaV2 are heteromeric, consisting of an α1 pore-forming subunit, associated with auxiliary CaVβ α2δ subunits. subunits encoded in mammals by four genes, CACNA2D1-4. They play important roles trafficking function the CaV channel complexes. Here we report biallelic variants CACNA2D1, encoding α2δ-1 protein, two unrelated individuals showing a developmental epileptic encephalopathy. Patient 1 has homozygous frameshift variant c.818_821dup/p.(Ser275Asnfs*13) resulting nonsense-mediated mRNA decay CACNA2D1 transcripts, absence protein detected patient-derived fibroblasts. 2 is compound heterozygous for early c.13_23dup/p.(Leu9Alafs*5), highly probably representing null allele missense c.626G>A/p.(Gly209Asp). Our functional studies show that this amino-acid change severely impairs as strongly reduced α2δ-1G209D to cell surface complete inability increase channels. Thus, loss-of-function underlie severe neurodevelopmental disorder these patients. results demonstrate critical importance non-interchangeability other proteins normal human neuronal development.

Language: Английский

Citations

Signal binding at both modules of its dCache domain enables the McpA chemoreceptor of Bacillus velezensis to sense different ligands DOI

Haichao Feng,

Yu Lv,

Tino Krell

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(29)

Published: July 13, 2022

Bacteria have evolved multiple signal transduction systems that permit an adaptation to changing environmental conditions. Chemoreceptor-based signaling cascades are very abundant in bacteria and among the most complex systems. Currently, our knowledge on molecular features determine recognition at chemoreceptors is limited. Chemoreceptor McpA of Bacillus velezensis SQR9 has been shown mediate chemotaxis a broad range different ligands. Here we show its ligand binding domain binds directly 13 chemoattractants. We provide support organic acids amino bind membrane-distal membrane-proximal module dCache domain, respectively, whereas sugars/sugar alcohols occurred both modules. Structural biology studies combined with site-directed mutagenesis experiments permitted identify 10 acid residues play key roles Residues regions were central for sensing amimo acids, all participated alcohol sensing. Most characterized possess narrow well-defined spectrum. propose here mechanism involving modules allows integration diverse signals by single chemoreceptor.

Language: Английский

Citations

Structural basis for CaVα2δ:gabapentin binding DOI

Zhou Chen, Abhisek Mondal, Daniel L. Minor

et al.

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 30(6), P. 735 - 739

Published: March 27, 2023

Language: Английский

Citations

The Voltage-Gated Calcium Channel α2δ Subunit in Neuropathic Pain DOI

Sheng-Jie Guo,

Yu-Qin Shi,

Ya-Nan Zheng

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 13, 2024

Language: Английский

Citations