Localizing the Charged Side Chains of Ion Channels within the Crowded Charge Models

2012 ◽  
Vol 9 (1) ◽  
pp. 766-773 ◽  
Author(s):  
Justin J. Finnerty ◽  
Robert Eisenberg ◽  
Paolo Carloni
Keyword(s):  
Ion Channels ◽  
Side Chains

scholarly journals Primary structure of peptides and ion channels. Role of amino acid side chains in voltage gating of melittin channels

1990 ◽  
Vol 58 (6) ◽  
pp. 1367-1375 ◽  
Author(s):  
M.T. Tosteson ◽  
O. Alvarez ◽  
W. Hubbell ◽  
R.M. Bieganski ◽  
C. Attenbach ◽  
...  
Keyword(s):  
Amino Acid ◽  
Ion Channels ◽  
Primary Structure ◽  
Voltage Gating ◽  
Side Chains ◽  
Amino Acid Side Chains

scholarly journals Identifying the elusive link between amino acid sequence and charge selectivity in pentameric ligand-gated ion channels

2016 ◽  
Vol 113 (45) ◽  
pp. E7106-E7115 ◽  
Author(s):  
Gisela D. Cymes ◽  
Claudio Grosman
Keyword(s):  
Ion Channels ◽  
Careful Analysis ◽  
Side Chains ◽  
Electrophysiological Recordings ◽  
Charge Selectivity ◽  
The Many ◽  
Backbone Atoms ◽  
Charge Sign ◽  
Gated Ion Channels ◽  
Ligand Gated Ion Channels

Among neurotransmitter-gated ion channels, the superfamily of pentameric ligand-gated ion channels (pLGICs) is unique in that its members display opposite permeant-ion charge selectivities despite sharing the same structural fold. Although much effort has been devoted to the identification of the mechanism underlying the cation-versus-anion selectivity of these channels, a careful analysis of past work reveals that discrepancies exist, that different explanations for the same phenomenon have often been put forth, and that no consensus view has yet been reached. To elucidate the molecular basis of charge selectivity for the superfamily as a whole, we performed extensive mutagenesis and electrophysiological recordings on six different cation-selective and anion-selective homologs from vertebrate, invertebrate, and bacterial origin. We present compelling evidence for the critical involvement of ionized side chains—whether pore-facing or buried—rather than backbone atoms and propose a mechanism whereby not only their charge sign but also their conformation determines charge selectivity. Insertions, deletions, and residue-to-residue mutations involving nonionizable residues in the intracellular end of the pore seem to affect charge selectivity by changing the rotamer preferences of the ionized side chains in the first turn of the M2 α-helices. We also found that, upon neutralization of the charged residues in the first turn of M2, the control of charge selectivity is handed over to the many other ionized side chains that decorate the pore. This explains the long-standing puzzle as to why the neutralization of the intracellular-mouth glutamates affects charge selectivity to markedly different extents in different cation-selective pLGICs.

scholarly journals A flexible GAS belt responds to pore mutations changing the ion selectivity of proton-gated channels

2021 ◽  
Vol 154 (1) ◽  
Author(s):  
Zhuyuan Chen ◽  
Sheng Lin ◽  
Tianze Xie ◽  
Jin-Ming Lin ◽  
Cecilia M. Canessa
Keyword(s):  
Ion Channels ◽  
Pore Structure ◽  
Ion Selectivity ◽  
Hydration Shell ◽  
Postsynaptic Membrane ◽  
Membrane Depolarization ◽  
Side Chains ◽  
Open Conformation ◽  
Central Pore ◽  
Close Fit

Proton-gated ion channels conduct mainly Na+ to induce postsynaptic membrane depolarization. Finding the determinants of ion selectivity requires knowledge of the pore structure in the open conformation, but such information is not yet available. Here, the open conformation of the hASIC1a channel was computationally modeled, and functional effects of pore mutations were analyzed in light of the predicted structures. The open pore structure shows two constrictions of similar diameter formed by the backbone of the GAS belt and, right beneath it, by the side chains of H28 from the reentrant loop. Models of nonselective mutant channels, but not those that maintain ion selectivity, predict enlargement of the GAS belt, suggesting that this motif is quite flexible and that the loss of stabilizing interactions in the central pore leads to changes in size/shape of the belt. Our results are consistent with the “close-fit” mechanism governing selectivity of hASIC1a, wherein the backbone of the GAS substitutes at least part of the hydration shell of a permeant ion to enable crossing the pore constriction.

Metal bridges to probe membrane ion channel structure and function

2015 ◽  
Vol 6 (3) ◽  
pp. 191-203 ◽  
Author(s):  
Paul Linsdell
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Conformational Changes ◽  
Three Dimensional ◽  
Structure And Function ◽  
Side Chains ◽  
Channel Protein ◽  
Conformational Rearrangements ◽  
And Function ◽  
Different Parts

AbstractIon channels are integral membrane proteins that undergo important conformational changes as they open and close to control transmembrane flux of different ions. The molecular underpinnings of these dynamic conformational rearrangements are difficult to ascertain using current structural methods. Several functional approaches have been used to understand two- and three-dimensional dynamic structures of ion channels, based on the reactivity of the cysteine side-chain. Two-dimensional structural rearrangements, such as changes in the accessibility of different parts of the channel protein to the bulk solution on either side of the membrane, are used to define movements within the permeation pathway, such as those that open and close ion channel gates. Three-dimensional rearrangements – in which two different parts of the channel protein change their proximity during conformational changes – are probed by cross-linking or bridging together two cysteine side-chains. Particularly useful in this regard are so-called metal bridges formed when two or more cysteine side-chains form a high-affinity binding site for metal ions such as Cd2+ or Zn2+. This review describes the use of these different techniques for the study of ion channel dynamic structure and function, including a comprehensive review of the different kinds of conformational rearrangements that have been studied in different channel types via the identification of intra-molecular metal bridges. Factors that influence the affinities and conformational sensitivities of these metal bridges, as well as the kinds of structural inferences that can be drawn from these studies, are also discussed.

A highly stable membrane for vanadium flow batteries (VFBs) enabled by the selective degradation of ionic side chains

2022 ◽  
Author(s):  
Ziming Zhao ◽  
Qing Dai ◽  
Xiaofeng Li ◽  
Suobo Zhang ◽  
Shenghai Li ◽  
...  
Keyword(s):  
Ion Channels ◽  
Side Chains ◽  
Selective Degradation ◽  
Flow Batteries

The side chains detach from the main chains of polymers, which leads to a transition of ion channels to micropores.

scholarly journals The amyloid concentric β-barrel hypothesis: models of Synuclein oligomers, annular protofibrils, lipoproteins, and transmembrane channels

2021 ◽  
Author(s):  
Stewart R. Durell ◽  
H. Robert Guy
Keyword(s):  
Ion Channels ◽  
Molecular Structures ◽  
Atomic Scale ◽  
Side Chains ◽  
Salt Bridges ◽  
Solvent Exposure ◽  
Homologous Proteins ◽  
Protein Surfaces ◽  
Molecular Weights ◽  
Aqueous Solvent

AbstractAmyloid beta (Aβ of Alzheimer’s disease) and α-synuclein (α-Syn of Parkinson’s disease) form large fibrils. Evidence is increasing however that much smaller oligomers are more toxic and that these oligomers can form transmembrane ion channels. We have proposed previously that Aβ42 oligomers, annular protofibrils, and ion channels adopt concentric β-barrel molecular structures. Here we extend that hypothesis to the superfamily of α, β, and γ-synucleins. Our models of numerous Synuclein oligomers, annular protofibrils, tubular protofibrils, lipoproteins, and ion channels were developed to be consistent with sizes, shapes, molecular weights, and secondary structures of assemblies as determined by EM and other studies. The models have the following features: 1) all subunits have identical structures and interactions; 2) they are consistent with conventional β-barrel theory; 3) the distance between walls of adjacent β-barrels is between 0.6 and 1.2 nm; 4) hydrogen bonds, salt bridges, interactions among aromatic side-chains, burial and tight packing of hydrophobic side-chains, and aqueous solvent exposure of hydrophilic side-chains are relatively optimal; and 5) residues that are identical among distantly related homologous proteins cluster in the interior of most oligomers whereas residues that are hypervariable are exposed on protein surfaces. Atomic scale models of some assemblies were developed.

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