Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cork-in-Bottle Occlusion of Fluoride Ion Channels by Crystallization Chaperones.

ABSTRACT: Crystallization of dual-topology fluoride (Fluc) channels requires small, soluble crystallization chaperones known as monobodies, which act as primary crystal lattice contacts. Previous structures of Flucs have been solved in the presence of monobodies that inhibit fluoride currents in single-channel electrophysiological recordings. These structures have revealed two-fold symmetric, doubly bound arrangements, with one monobody on each side of the membrane. The combined electrophysiological and structural observations raise the possibility that chaperone binding allosterically closes the channel, altering the structure from its conducting form. To address this, we identify and solve the structure with a different monobody that only partially blocks fluoride currents. The structure of the channel-monobody complex is asymmetric, with monobody bound to one side of the channel only. The channel conformation is nearly identical on the bound and uncomplexed sides, and to all previously solved structures, providing direct structural evidence that monobody binding does not induce local structural changes.

SUBMITTER: McIlwain BC

PROVIDER: S-EPMC5884710 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Ion permeation, selectivity, and electronic polarization in fluoride channels.

Project description:Fluoride channels (Flucs) export toxic F- from the cytoplasm. Crystallography and mutagenesis have identified several conserved residues crucial for fluoride transport, but the permeation mechanism at the molecular level has remained elusive. Herein, we have applied constant-pH molecular dynamics and free-energy-sampling methods to investigate fluoride permeation through a Fluc protein from Escherichia coli. We find that fluoride is facile to permeate in its charged form, i.e., F-, by traversing through a non-bonded network. The extraordinary F- selectivity is gained by the hydrogen-bonding capability of the central binding site and the Coulombic filter at the channel entrance. The F- permeation rate calculated using an electronically polarizable force field is significantly more accurate compared with the experimental value than that calculated using a more standard additive force field, suggesting an essential role for electronic polarization in the F--Fluc interactions.

| S-EPMC9034187 | biostudies-literature

Cork-in-bottle mechanism of inhibitor binding to mammalian complex I.

Project description:Mitochondrial complex I (NADH:ubiquinone oxidoreductase), a major contributor of free energy for oxidative phosphorylation, is increasingly recognized as a promising drug target for ischemia-reperfusion injury, metabolic disorders, and various cancers. Several pharmacologically relevant but structurally unrelated small molecules have been identified as specific complex I inhibitors, but their modes of action remain unclear. Here, we present a 3.0-Å resolution cryo-electron microscopy structure of mammalian complex I inhibited by a derivative of IACS-010759, which is currently in clinical development against cancers reliant on oxidative phosphorylation, revealing its unique cork-in-bottle mechanism of inhibition. We combine structural and kinetic analyses to deconvolute cross-species differences in inhibition and identify the structural motif of a "chain" of aromatic rings as a characteristic that promotes inhibition. Our findings provide insights into the importance of π-stacking residues for inhibitor binding in the long substrate-binding channel in complex I and a guide for future biorational drug design.

| S-EPMC8121435 | biostudies-literature

Engineering of recombinant crystallization chaperones.

Project description:The preparation of diffraction quality crystals remains the major bottleneck in macromolecular X-ray crystallography. A crystallization chaperone is an auxiliary protein, such as fragments of monoclonal antibodies, that binds to and increases the crystallization probability of a target molecule of interest. Such chaperones reduce conformational heterogeneity, mask counterproductive surfaces while extending surfaces predisposed to forming crystal contacts, and provide phasing information. Crystallization chaperones generated using recombinant technologies have emerged as superior alternatives that increase the throughput and eliminate inherent limitations associated with antibody production by animal immunization and the hybridoma technology.

| S-EPMC2736338 | biostudies-literature

Fast and selective fluoride ion conduction in sub-1-nanometer metal-organic framework channels.

Project description:Biological fluoride ion channels are sub-1-nanometer protein pores with ultrahigh F- conductivity and selectivity over other halogen ions. Developing synthetic F- channels with biological-level selectivity is highly desirable for ion separations such as water defluoridation, but it remains a great challenge. Here we report synthetic F- channels fabricated from zirconium-based metal-organic frameworks (MOFs), UiO-66-X (X = H, NH2, and N+(CH3)3). These MOFs are comprised of nanometer-sized cavities connected by sub-1-nanometer-sized windows and have specific F- binding sites along the channels, sharing some features of biological F- channels. UiO-66-X channels consistently show ultrahigh F- conductivity up to ~10 S m-1, and ultrahigh F-/Cl- selectivity, from ~13 to ~240. Molecular dynamics simulations reveal that the ultrahigh F- conductivity and selectivity can be ascribed mainly to the high F- concentration in the UiO-66 channels, arising from specific interactions between F- ions and F- binding sites in the MOF channels.

| S-EPMC6560108 | biostudies-literature

An Interfacial Sodium Ion is an Essential Structural Feature of Fluc Family Fluoride Channels.

Project description:Fluc family fluoride channels are assembled as primitive antiparallel homodimers. Crystallographic studies revealed a cation bound at the center of the protein, where it is coordinated at the dimer interface by main chain carbonyl oxygen atoms from the midmembrane breaks in two corresponding transmembrane helices. Here, we show that this cation is a stably bound sodium ion, and although it is not a transported substrate, its presence is required for the channel to adopt an open, fluoride-conducting conformation. The interfacial site is selective for sodium over other cations, except for Li+, which competes with Na+ for binding, but does not support channel activity. The strictly structural role fulfilled by this sodium provides new context to understand the structures, mechanisms, and evolutionary origins of widespread Na+-coupled transporters.

| S-EPMC7054162 | biostudies-literature

Genomic profile of transporters and ion channels

Project description:Genomic profile of transporters and ion channels in differentiated or undifferentiated Caco-2 cells grown for 5 days, 1 week, 2 weeks or 3 weeks in flasks or filters Keywords: ordered

2004-05-08 | GSE1368 | GEO

Cork-Derived Carbon Sheets for High-Performance Na-Ion Capacitors

Project description:S-doped carbon sheets have been easily prepared by deconstructing

| S-EPMC10431350 | biostudies-literature

Membrane Exporters of Fluoride Ion.

Project description:Microorganisms contend with numerous and unusual chemical threats and have evolved a catalog of resistance mechanisms in response. One particularly ancient, pernicious threat is posed by fluoride ion (F-), a common xenobiotic in natural environments that causes broad-spectrum harm to metabolic pathways. This review focuses on advances in the last ten years toward understanding the microbial response to cytoplasmic accumulation of F-, with a special emphasis on the structure and mechanisms of the proteins that microbes use to export fluoride: the CLCF family of F-/H+ antiporters and the Fluc/FEX family of F- channels.

| S-EPMC8217344 | biostudies-literature

Ion Channels

Project description: Not available

| S-EPMC3315630 | biostudies-literature

The fluoride permeation pathway and anion recognition in Fluc family fluoride channels.

Project description:Fluc family fluoride channels protect microbes against ambient environmental fluoride by undermining the cytoplasmic accumulation of this toxic halide. These proteins are structurally idiosyncratic, and thus the permeation pathway and mechanism have no analogy in other known ion channels. Although fluoride-binding sites were identified in previous structural studies, it was not evident how these ions access aqueous solution, and the molecular determinants of anion recognition and selectivity have not been elucidated. Using x-ray crystallography, planar bilayer electrophysiology, and liposome-based assays, we identified additional binding sites along the permeation pathway. We used this information to develop an oriented system for planar lipid bilayer electrophysiology and observed anion block at one of these sites, revealing insights into the mechanism of anion recognition. We propose a permeation mechanism involving alternating occupancy of anion-binding sites that are fully assembled only as the substrate approaches.

| S-EPMC8315801 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data