Regulatory γ1 subunits defy symmetry in functional modulation of BK channels.

Abstract:

:Structural symmetry is a hallmark of homomeric ion channels. Nonobligatory regulatory proteins can also critically define the precise functional role of such channels. For instance, the pore-forming subunit of the large conductance voltage and calcium-activated potassium (BK, Slo1, or KCa1.1) channels encoded by a single KCa1.1 gene assembles in a fourfold symmetric fashion. Functional diversity arises from two families of regulatory subunits, β and γ, which help define the range of voltages over which BK channels in a given cell are activated, thereby defining physiological roles. A BK channel can contain zero to four β subunits per channel, with each β subunit incrementally influencing channel gating behavior, consistent with symmetry expectations. In contrast, a γ1 subunit (or single type of γ1 subunit complex) produces a functionally all-or-none effect, but the underlying stoichiometry of γ1 assembly and function remains unknown. Here we utilize two distinct and independent methods, a Forster resonance energy transfer-based optical approach and a functional reporter in single-channel recordings, to reveal that a BK channel can contain up to four γ1 subunits, but a single γ1 subunit suffices to induce the full gating shift. This requires that the asymmetric association of a single regulatory protein can act in a highly concerted fashion to allosterically influence conformational equilibria in an otherwise symmetric K+ channel.

authors

Gonzalez-Perez V,Ben Johny M,Xia XM,Lingle CJ

doi

10.1073/pnas.1804560115

subject

Has Abstract

pub_date

2018-10-02 00:00:00

pages

9923-9928

issue

40

eissn

0027-8424

issn

1091-6490

pii

1804560115

journal_volume

115

pub_type

杂志文章
  • Checkpoints in the progression of autoimmune disease: lessons from diabetes models.

    abstract::In the last few years, data from experiments employing transgenic models of autoimmune disease have strengthened a particular concept of autoimmunity: disease results not so much from cracks in tolerance induction systems, leading to the generation of anti-self repertoire, as from the breakdown of secondary systems th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.93.6.2260

    authors: André I,Gonzalez A,Wang B,Katz J,Benoist C,Mathis D

    更新日期:1996-03-19 00:00:00

  • Potent inhibition of huntingtin aggregation and cytotoxicity by a disulfide bond-free single-domain intracellular antibody.

    abstract::Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the number of polyglutamine-encoding CAG repeats in the gene that encodes the huntingtin (htt) protein. A property of the mutant protein that is intimately involved in the development of the disease is the propensity of the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0408134101

    authors: Colby DW,Chu Y,Cassady JP,Duennwald M,Zazulak H,Webster JM,Messer A,Lindquist S,Ingram VM,Wittrup KD

    更新日期:2004-12-21 00:00:00

  • Male dominance rarely skews the frequency distribution of Y chromosome haplotypes in human populations.

    abstract::A central tenet of evolutionary social science holds that behaviors, such as those associated with social dominance, produce fitness effects that are subject to cultural selection. However, evidence for such selection is inconclusive because it is based on short-term statistical associations between behavior and ferti...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0710158105

    authors: Lansing JS,Watkins JC,Hallmark B,Cox MP,Karafet TM,Sudoyo H,Hammer MF

    更新日期:2008-08-19 00:00:00

  • Reconstruction of bacteriophage T4 DNA replication apparatus from purified components: rolling circle replication following de novo chain initiation on a single-stranded circular DNA template.

    abstract::The protein products of T4 bacteriophage genes 41, 43, 45, 44, and 62 have been purified to near homogeneity using an assay which measures their stimulation of DNA synthesis in a crude lysate of Escherichia coli cells in fected by an appropriate mutant phage. When all of these proteins and T4 gene 32 protein are incub...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.12.4800

    authors: Morris CF,Sinha NK,Alberts BM

    更新日期:1975-12-01 00:00:00

  • Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis.

    abstract::RPE65 is a protein of unknown function expressed specifically by the retinal pigment epithelium. We examined all 14 exons of this gene in 147 unrelated patients with autosomal recessive retinitis pigmentosa (RP), in 15 patients with isolate RP, and in 45 patients with Leber congenital amaurosis (LCA). Sequence anomali...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.6.3088

    authors: Morimura H,Fishman GA,Grover SA,Fulton AB,Berson EL,Dryja TP

    更新日期:1998-03-17 00:00:00

  • Rudimentary form of cellular "vision".

    abstract::BHK cells were inoculated sparsely on one face ("sparse- or s-face") of a thin glass film whose opposite face was covered with a 2- to 3-day-old confluent layer of BHK cells ("confluent- or c-face"). After 7 hr of attaching and spreading in the absence of visible light, most of the cells on the s-face traversed with t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.17.8288

    authors: Albrecht-Buehler G

    更新日期:1992-09-01 00:00:00

  • Cellular studies of auditory hair cell regeneration in birds.

    abstract::A decade ago it was discovered that mature birds are able to regenerate hair cells, the receptors for auditory perception. This surprising finding generated hope in the field of auditory neuroscience that new hair cells someday may be coaxed to form in another class of warm-blooded vertebrates, mammals. We have made c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.22.11714

    authors: Stone JS,Rubel EW

    更新日期:2000-10-24 00:00:00

  • Transcription of histone H4, H3, and H1 cell cycle genes: promoter factor HiNF-D contains CDC2, cyclin A, and an RB-related protein.

    abstract::Cell cycle-controlled human histone genes are coordinately expressed during S phase, and transcriptional regulation involves a series of trans-acting factors (HiNFs). The proliferation-specific factor HiNF-D interacts with multiple recognition motifs in histone H4, H3, and H1 promoters. Using gel shift immunoassays, w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.26.12882

    authors: van Wijnen AJ,Aziz F,Graña X,De Luca A,Desai RK,Jaarsveld K,Last TJ,Soprano K,Giordano A,Lian JB

    更新日期:1994-12-20 00:00:00

  • An antigen in Hodgkin's disease tissue cultures: radioiodine-labeled antibody studies.

    abstract::An antiserum was prepared in rabbits against an antigen obtained by density gradient sedimentation of centrifuged medium from monolayer cultures of spleens involved by Hodgkin's disease. The antiserum was tested by isotopic antibody techniques with cells from each of eight cultures derived from spleens involved by Hod...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.7.2605

    authors: Long JC,Aisenberg AC,Zamecnik PC

    更新日期:1974-07-01 00:00:00

  • Functional neuroanatomy of antisaccade eye movements investigated with positron emission tomography.

    abstract::Increasing interest in the role of the frontal lobe in relation to psychiatric and neurologic disorders has popularized tests of frontal function. One of these is the antisaccade task, in which both frontal lobe patients and schizophrenics are impaired despite normal performance on (pro)saccadic tasks. We used positio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.3.925

    authors: O'Driscoll GA,Alpert NM,Matthysse SW,Levy DL,Rauch SL,Holzman PS

    更新日期:1995-01-31 00:00:00

  • Membrane integration of an essential β-barrel protein prerequires burial of an extracellular loop.

    abstract::The Bam complex assembles β-barrel proteins into the outer membrane (OM) of Gram-negative bacteria. These proteins comprise cylindrical β-sheets with long extracellular loops and create pores to allow passage of nutrients and waste products across the membrane. Despite their functional importance, several questions re...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1616576114

    authors: Wzorek JS,Lee J,Tomasek D,Hagan CL,Kahne DE

    更新日期:2017-03-07 00:00:00

  • Definition of a physiologic aging autoantigen by using synthetic peptides of membrane protein band 3: localization of the active antigenic sites.

    abstract::Senescent cell antigen (SCA), an aging antigen, is a protein that appears on old cells and marks them for removal by the immune system in mammals. It is derived from band 3, a ubiquitous membrane transport protein found in diverse cell types and tissues. We have used synthetic peptides to identify aging antigenic site...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.15.5734

    authors: Kay MM,Marchalonis JJ,Hughes J,Watanabe K,Schluter SF

    更新日期:1990-08-01 00:00:00

  • Fc epsilon RI-mediated tyrosine phosphorylation and activation of the 72-kDa protein-tyrosine kinase, PTK72, in RBL-2H3 rat tumor mast cells.

    abstract::In RBL-2H3 rat tumor mast cells, cross-linking the high-affinity IgE receptor Fc epsilon RI causes tyrosine phosphorylation of multiple proteins. These phosphoproteins include phospholipase C gamma 1, the beta and gamma subunits of the Fc epsilon RI, the Src family protein-tyrosine kinase Lyn, and a 72-kDa protein tha...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.19.9107

    authors: Hutchcroft JE,Geahlen RL,Deanin GG,Oliver JM

    更新日期:1992-10-01 00:00:00

  • Specific gangliosides function as host cell receptors for Sendai virus.

    abstract::The ability of specific gangliosides to function as host cell receptors for Sendai virus was investigated by using Madin-Darby bovine kidney cells which become resistant to infection upon treatment with Vibrio cholerae sialidase. Sialidase-treated cells were incubated for 20 min at 37 degrees C with individual, highly...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.9.5406

    authors: Markwell MA,Svennerholm L,Paulson JC

    更新日期:1981-09-01 00:00:00

  • Three-dimensional model of the active site of the self-splicing rRNA precursor of Tetrahymena.

    abstract::The rRNA intervening sequence of Tetrahymena is a catalytic RNA molecule, or "ribozyme." A tertiary-structure model of the active site of this ribozyme has been constructed based on comparative sequence analysis of related group I intervening sequences, data on the accessibility of each nucleotide to chemical and enzy...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.24.8788

    authors: Kim SH,Cech TR

    更新日期:1987-12-01 00:00:00

  • The entropic contributions in vitamin B12 enzymes still reflect the electrostatic paradigm.

    abstract::The catalytic power of enzymes containing coenzyme B12 has been, in some respects, the "last bastion" for the strain hypothesis. Our previous study of this system established by a careful sampling that the major part of the catalytic effect is due to the electrostatic interaction between the ribose of the ado group an...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1503828112

    authors: Schopf P,Mills MJ,Warshel A

    更新日期:2015-04-07 00:00:00

  • Poly(A) polymerase and poly(g) polymerase in wheat chloroplasts.

    abstract::Extracts of wheat chloroplasts contain a poly(A) polymerase which can polymerize AMP residues from ATP onto an RNA primer. Whole extracts of wheat leaves also contain another poly(A) polymerase which is present in much larger amount and is probably derived from the nuclei. Both polymerases can utilize as primer poly(A...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.2.389

    authors: Burkard G,Keller EB

    更新日期:1974-02-01 00:00:00

  • Astrocyte elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis.

    abstract::Astrocyte-elevated gene-1 (AEG-1) expression is increased in multiple cancers and plays a central role in Ha-ras-mediated oncogenesis through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Additionally, overexpression of AEG-1 protects primary and transformed human and rat cells from serum starvation-...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0910936106

    authors: Emdad L,Lee SG,Su ZZ,Jeon HY,Boukerche H,Sarkar D,Fisher PB

    更新日期:2009-12-15 00:00:00

  • Variable genetic architectures produce virtually identical molecules in bacterial symbionts of fungus-growing ants.

    abstract::Small molecules produced by Actinobacteria have played a prominent role in both drug discovery and organic chemistry. As part of a larger study of the actinobacterial symbionts of fungus-growing ants, we discovered a small family of three previously unreported piperazic acid-containing cyclic depsipeptides, gerumycins...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1515348112

    authors: Sit CS,Ruzzini AC,Van Arnam EB,Ramadhar TR,Currie CR,Clardy J

    更新日期:2015-10-27 00:00:00

  • Direct observation of turbulent magnetic fields in hot, dense laser produced plasmas.

    abstract::Turbulence in fluids is a ubiquitous, fascinating, and complex natural phenomenon that is not yet fully understood. Unraveling turbulence in high density, high temperature plasmas is an even bigger challenge because of the importance of electromagnetic forces and the typically violent environments. Fascinating and nov...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1200753109

    authors: Mondal S,Narayanan V,Ding WJ,Lad AD,Hao B,Ahmad S,Wang WM,Sheng ZM,Sengupta S,Kaw P,Das A,Kumar GR

    更新日期:2012-05-22 00:00:00

  • K63 ubiquitylation triggers proteasomal degradation by seeding branched ubiquitin chains.

    abstract::Different polyubiquitin chain linkages direct substrates toward distinct cellular pathways. K63-linked ubiquitylation is known to regulate proteasome-independent events such as signal transduction, but its function in the context of heterogeneous ubiquitin chains remains unclear. Here, we report that K63 ubiquitylatio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1716673115

    authors: Ohtake F,Tsuchiya H,Saeki Y,Tanaka K

    更新日期:2018-02-13 00:00:00

  • Mouse numb is an essential gene involved in cortical neurogenesis.

    abstract::During neurogenesis of the mammalian neocortex, neural progenitor cells divide to generate daughter cells that either become neurons or remain as progenitor cells. The mouse numb (m-numb) gene encodes a membrane-associated protein that is asymmetrically localized to the apical cell membrane of dividing cortical progen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.12.6844

    authors: Zhong W,Jiang MM,Schonemann MD,Meneses JJ,Pedersen RA,Jan LY,Jan YN

    更新日期:2000-06-06 00:00:00

  • BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon.

    abstract::The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly und...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1616363114

    authors: Farías GG,Guardia CM,De Pace R,Britt DJ,Bonifacino JS

    更新日期:2017-04-04 00:00:00

  • Flanking nuclear matrix attachment regions synergize with the T cell receptor delta enhancer to promote V(D)J recombination.

    abstract::Previous studies have identified nuclear matrix attachment regions (MARs) that are closely associated with transcriptional enhancers in the IgH, Igkappa, and T cell receptor (TCR) beta loci, but have yielded conflicting information regarding their functional significance. In this report, a combination of in vitro and ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.21.11970

    authors: Zhong XP,Carabaña J,Krangel MS

    更新日期:1999-10-12 00:00:00

  • A small-molecule therapeutic lead for Huntington's disease: preclinical pharmacology and efficacy of C2-8 in the R6/2 transgenic mouse.

    abstract::Huntington's disease (HD) is a progressive neurodegenerative disease caused by a glutamine expansion within huntingtin protein. The exact pathological mechanisms determining disease onset and progression remain unclear. However, aggregates of insoluble mutant huntingtin (mhtt), a hallmark of HD, are readily detected w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0707842104

    authors: Chopra V,Fox JH,Lieberman G,Dorsey K,Matson W,Waldmeier P,Housman DE,Kazantsev A,Young AB,Hersch S

    更新日期:2007-10-16 00:00:00

  • Structure of columns in monkey striate cortex induced by luminant-contrast and color-contrast stimulation.

    abstract::Color and black and white line stimulation produce qualitatively and quantitatively different 2-deoxy[14C]glucose column patterns in the striate cortex of macaque monkeys. Microdensitometry of these stimulus-dependent columns reveals interlaminar density differences that serve as a signature for the stimulus condition...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.21.6722

    authors: Crawford ML,Meharg LS,Johnston DA

    更新日期:1982-11-01 00:00:00

  • Regulated expression of endonuclease EcoRI in Saccharomyces cerevisiae: nuclear entry and biological consequences.

    abstract::In an investigation to determine how proteins are localized within the nucleus of a cell, we demonstrate that the restriction endonuclease EcoRI is able to enter and function within the nucleus of Saccharomyces cerevisiae when this prokaryotic protein is synthesized in vivo. The EcoRI endonuclease was produced in yeas...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.5.1354

    authors: Barnes G,Rine J

    更新日期:1985-03-01 00:00:00

  • The chloroplast and mitochondrial genome sequences of the charophyte Chaetosphaeridium globosum: insights into the timing of the events that restructured organelle DNAs within the green algal lineage that led to land plants.

    abstract::The land plants and their immediate green algal ancestors, the charophytes, form the Streptophyta. There is evidence that both the chloroplast DNA (cpDNA) and mitochondrial DNA (mtDNA) underwent substantial changes in their architecture (intron insertions, gene losses, scrambling in gene order, and genome expansion in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.162203299

    authors: Turmel M,Otis C,Lemieux C

    更新日期:2002-08-20 00:00:00

  • Function and glycosylation of plant-derived antiviral monoclonal antibody.

    abstract::Plant genetic engineering led to the production of plant-derived mAb (mAbP), which provides a safe and economically feasible alternative to the current methods of antibody production in animal systems. In this study, the heavy and light chains of human anti-rabies mAb were expressed and assembled in planta under the c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0832472100

    authors: Ko K,Tekoah Y,Rudd PM,Harvey DJ,Dwek RA,Spitsin S,Hanlon CA,Rupprecht C,Dietzschold B,Golovkin M,Koprowski H

    更新日期:2003-06-24 00:00:00

  • Boosting medical diagnostics by pooling independent judgments.

    abstract::Collective intelligence refers to the ability of groups to outperform individual decision makers when solving complex cognitive problems. Despite its potential to revolutionize decision making in a wide range of domains, including medical, economic, and political decision making, at present, little is known about the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1601827113

    authors: Kurvers RH,Herzog SM,Hertwig R,Krause J,Carney PA,Bogart A,Argenziano G,Zalaudek I,Wolf M

    更新日期:2016-08-02 00:00:00