The Josephin domain determines the morphological and mechanical properties of ataxin-3 fibrils.

Abstract:

:Fibrillar aggregation of the protein ataxin-3 is linked to the inherited neurodegenerative disorder Spinocerebellar ataxia type 3, a member of the polyQ expansion disease family. We previously reported that aggregation and stability of the nonpathological form of ataxin-3, carrying an unexpanded polyQ tract, are modulated by its N-terminal Josephin domain. It was also shown that expanded ataxin-3 aggregates via a two-stage mechanism initially involving Josephin self-association, followed by a polyQ-dependent step. Despite this recent progress, however, the exact mechanism of ataxin-3 fibrilization remains elusive. Here, we have used electron microscopy, atomic force microscopy, and other biophysical techniques to characterize the morphological and mechanical properties of nonexpanded ataxin-3 fibrils. By comparing aggregates of ataxin-3 and of the isolated Josephin domain, we show that the two proteins self-assemble into fibrils with markedly similar features over the temperature range 37-50°C. Estimates of persistence length and Young's modulus of the fibrils reveal a great flexibility. Our data indicate that, under physiological conditions, during early aggregation Josephin retains a nativelike secondary structure but loses its enzymatic activity. The results suggest a key role of Josephin in ataxin-3 fibrillar aggregation.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Masino L,Nicastro G,De Simone A,Calder L,Molloy J,Pastore A

doi

10.1016/j.bpj.2011.02.056

subject

Has Abstract

pub_date

2011-04-20 00:00:00

pages

2033-42

issue

8

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(11)00309-2

journal_volume

100

pub_type

杂志文章
  • Model inspired by nuclear pore complex suggests possible roles for nuclear transport receptors in determining its structure.

    abstract::Nuclear transport receptors (NTRs) mediate nucleocytoplasmic transport via their affinity for unstructured proteins (polymers) in the nuclear pore complex (NPC). Here, we have modeled the effect of NTRs on polymeric structure in the nanopore confinement of the NPC central conduit. The model explicitly takes into accou...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2013.11.013

    authors: Osmanović D,Ford IJ,Hoogenboom BW

    更新日期:2013-12-17 00:00:00

  • The monovalent cation "leak" transport in human erythrocytes: an electroneutral exchange process.

    abstract::The mechanism of the "ground permeability" of the human erythrocyte membrane for K+ and Na+ was investigated with respect to a possible involvement of a previously unidentified specific transport pathway, because earlier studies showed that it cannot be explained on the basis of simple electrodiffusion. In particular,...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(97)78106-2

    authors: Richter S,Hamann J,Kummerow D,Bernhardt I

    更新日期:1997-08-01 00:00:00

  • Cooperative Clustering Digitizes Biochemical Signaling and Enhances its Fidelity.

    abstract::Many membrane-bound molecules in cells form small clusters. It has been hypothesized that these clusters convert an analog extracellular signal into a digital intracellular signal and that this conversion increases signaling fidelity. However, the mechanism by which clusters digitize a signal and the subsequent effect...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2016.02.031

    authors: Roob E 3rd,Trendel N,Rein Ten Wolde P,Mugler A

    更新日期:2016-04-12 00:00:00

  • Influence of Ganglioside GM1 Concentration on Lipid Clustering and Membrane Properties and Curvature.

    abstract::Gangliosides are a class of glycosphingolipids (GSLs) with amphiphilic character that are found at the outer leaflet of the cell membranes, where their ability to organize into special domains makes them vital cell membrane components. However, a molecular understanding of GSL-rich membranes in terms of their clustere...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2016.09.021

    authors: Patel DS,Park S,Wu EL,Yeom MS,Widmalm G,Klauda JB,Im W

    更新日期:2016-11-01 00:00:00

  • Deuterium magnetic resonance study of the gel and liquid crystalline phases of dipalmitoyl phosphatidylcholine.

    abstract::Deuterium magnetic resonance is applied to the study of the liquid crystalline and gel phases, and of the phase transition, of a multilamellar dispersion of chain perdeuterated (d62)-dipalmitoyl phosphatidylcholine/H2O. Analysis of the deuterium spectra in terms of the moments of the spectra allows one to make quantit...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(79)85222-4

    authors: Davis JH

    更新日期:1979-09-01 00:00:00

  • Temperature derivative fluorescence spectroscopy as a tool to study dynamical changes in protein crystals.

    abstract::Motions through the energy landscape of proteins lead to biological function. At temperatures below a dynamical transition (150-250 K), some of these motions are arrested and the activity of some proteins ceases. Here, we introduce the technique of temperature-derivative fluorescence microspectrophotometry to investig...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(04)74365-9

    authors: Weik M,Vernede X,Royant A,Bourgeois D

    更新日期:2004-05-01 00:00:00

  • Diffusion of extracellular K+ can synchronize bursting oscillations in a model islet of Langerhans.

    abstract::Electrical bursting oscillations of mammalian pancreatic beta-cells are synchronous among cells within an islet. While electrical coupling among cells via gap junctions has been demonstrated, its extent and topology are unclear. The beta-cells also share an extracellular compartment in which oscillations of K+ concent...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(93)81092-0

    authors: Stokes CL,Rinzel J

    更新日期:1993-08-01 00:00:00

  • Unique biphasic band shape of the visible circular dichroism of bacteriorhodopsin in purple membrane: Excitons, multiple transitions or protein heterogeneity?

    abstract::OVER A DECADE AND A HALF AGO, WHEN THE FIRST VISIBLE MEMBRANE SUSPENSION CIRCULAR DICHROIC (CD) SPECTRUM OF THE PURPLE MEMBRANE (PM) WAS PRESENTED, TWO MECHANISMS WERE PROPOSED TO ACCOUNT FOR THE OBSERVED BIPHASIC SHAPED CD BAND: (a) excitonic interactions among the retinals of the sole protein bacteriorhodopsin (bR) ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(92)81701-0

    authors: Cassim JY

    更新日期:1992-11-01 00:00:00

  • Electrical properties of dendritic spines with bulbous end terminals.

    abstract::Several suggestions have been made about the functional significance of dendritic spines in connection with synaptic plasticity. We investigated transient electrical behavior of spines with bulbous terminals in neurons with arbitrary dendritic geometries. It is shown that postsynaptic potential transform caused by a s...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(84)84008-4

    authors: Kawato M,Tsukahara N

    更新日期:1984-08-01 00:00:00

  • Theory of light quenching: effects of fluorescence polarization, intensity, and anisotropy decays.

    abstract::Experimental studies have recently demonstrated that fluorescence emission can be quenched by laser light pulses from modern high repetition rate lasers, a phenomenon we call "light quenching." We now describe the theory of light quenching and some of its effects on the steady-state and time-resolved intensity and ani...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(94)80686-1

    authors: Kuśba J,Bogdanov V,Gryczynski I,Lakowicz JR

    更新日期:1994-11-01 00:00:00

  • Phosphorylated Calmodulin Promotes PI3K Activation by Binding to the SH2 Domains.

    abstract::How calmodulin (CaM) acts in KRAS-driven cancers is a vastly important question. CaM binds to and stimulates PI3Kα/Akt signaling, promoting cell growth and proliferation. Phosphorylation of CaM at Tyr99 (pY99) enhances PI3Kα activation. PI3Kα is a lipid kinase. It phosphorylates PIP2 to produce PIP3, to which Akt bind...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2017.09.008

    authors: Zhang M,Jang H,Gaponenko V,Nussinov R

    更新日期:2017-11-07 00:00:00

  • A MOLECULAR STRUCTURAL BASIS FOR THE EXCITATION PROPERTIES OF AXONS.

    abstract::A structural model is suggested for axon membranes consisting of a double layer of lipid and phospholipid molecules in which the polar ends of certain phospholipids change their orientation and combining properties under the influence of an electric field. The phosphate groups act as ion exchange "gates" for the contr...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/s0006-3495(64)86776-x

    authors: GOLDMANN DE

    更新日期:1964-05-01 00:00:00

  • Glycosphingolipid fatty acid arrangement in phospholipid bilayers: cholesterol effects.

    abstract::Deuterium wide line NMR spectroscopy was used to study cholesterol effects on the ceramide portions of two glycosphingolipids (GSLs) distributed as minor components in fluid membranes. The common existence of very long fatty acids on GSLs was taken into account by including one glycolipid species with fatty acid chain...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(95)80173-6

    authors: Morrow MR,Singh D,Lu D,Grant CW

    更新日期:1995-01-01 00:00:00

  • Direct visualization of spruce budworm antifreeze protein interacting with ice crystals: basal plane affinity confers hyperactivity.

    abstract::Antifreeze proteins (AFPs) protect certain organisms from freezing by adhering to ice crystals, thereby preventing their growth. All AFPs depress the nonequilibrium freezing temperature below the melting point; however AFPs from overwintering insects, such as the spruce budworm (sbw) are 10-100 times more effective th...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.107.125328

    authors: Pertaya N,Marshall CB,Celik Y,Davies PL,Braslavsky I

    更新日期:2008-07-01 00:00:00

  • Direct observation of protein unfolded state compaction in the presence of macromolecular crowding.

    abstract::Proteins fold and function in cellular environments that are crowded with other macromolecules. As a consequence of excluded volume effects, compact folded states of proteins should be indirectly stabilized due to destabilization of extended unfolded conformations. Here, we assess the role of excluded volume in terms ...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2012.12.020

    authors: Mikaelsson T,Adén J,Johansson LB,Wittung-Stafshede P

    更新日期:2013-02-05 00:00:00

  • The electrical conductance of semipermeable membranes. I. A formal analysis.

    abstract::A kinetic analysis of membrane conductance under conditions of stationary flow is presented. The semipermeable membrane is idealized as a homogeneous laminar phase separating ionic solutions on either side. It is assumed, without consideration of the mechanisms involved, that some ion species permeate the membrane whi...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(65)86757-1

    authors: Bruner LJ

    更新日期:1965-11-01 00:00:00

  • The stiffness of the flagella of impaled bull sperm.

    abstract::The elastic rigidity (stiffness) of impaled motionless bull sperm flagella has been determined by a manipulatory technique which permitted direct analytical treatment of the experimental system. The effects of external ATP and ADP were measured. It was found that ATP acts as a plasticizing agent, while ADP does not. T...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(73)85997-1

    authors: Lindemann CB,Rudd WG,Rikmenspoel R

    更新日期:1973-05-01 00:00:00

  • Determining force dependence of two-dimensional receptor-ligand binding affinity by centrifugation.

    abstract::Analyses of receptor-ligand interactions are important to the understanding of cellular adhesion. Traditional methods of measuring the three-dimensional (3D) dissociation constant (Kd) require at least one of the molecular species in solution and hence cannot be directly applied to the case of cell adhesion. We descri...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(98)77807-5

    authors: Piper JW,Swerlick RA,Zhu C

    更新日期:1998-01-01 00:00:00

  • The extracellular electrical resistivity in cell adhesion.

    abstract::The interaction of cells in a tissue depends on the nature of the extracellular matrix. The electrical properties of the narrow extracellular space are unknown. Here we consider cell adhesion mediated by extracellular matrix protein on a solid substrate as a model system. We culture human embryonic kidney (HEK293) cel...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.105.072587

    authors: Gleixner R,Fromherz P

    更新日期:2006-04-01 00:00:00

  • Catalysis-enhancement via rotary fluctuation of F1-ATPase.

    abstract::Protein conformational fluctuations modulate the catalytic powers of enzymes. The frequency of conformational fluctuations may modulate the catalytic rate at individual reaction steps. In this study, we modulated the rotary fluctuation frequency of F1-ATPase (F1) by attaching probes with different viscous drag coeffic...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2013.09.050

    authors: Watanabe R,Hayashi K,Ueno H,Noji H

    更新日期:2013-11-19 00:00:00

  • The electronic structure of Fe2+ in reaction centers from Rhodopseudomonas sphaeroides. I. Static magnetization measurements.

    abstract::We have measured the static magnetization of unreduced and reduced reaction centers that vary in their quinone content. Measurements were performed in the temperature range 0.7 degrees K less than T less than 200 degrees K and magnetic fields of up to 10 kG. The electronic g-value, crystal field parameters D, E, and t...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(80)85030-2

    authors: Butler WF,Johnston DC,Shore HB,Fredkin DR,Okamura MY,Feher G

    更新日期:1980-12-01 00:00:00

  • Residues in Na(+) channel D3-S6 segment modulate both batrachotoxin and local anesthetic affinities.

    abstract::Batrachotoxin (BTX) alters the gating of voltage-gated Na(+) channels and causes these channels to open persistently, whereas local anesthetics (LAs) block Na(+) conductance. The BTX and LA receptors have been mapped to several common residues in D1-S6 and D4-S6 segments of the Na(+) channel alpha-subunit. We substitu...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(00)76390-9

    authors: Wang SY,Nau C,Wang GK

    更新日期:2000-09-01 00:00:00

  • Modeling of Transmembrane Potential in Realistic Multicellular Structures before Electroporation.

    abstract::Many approaches for studying the transmembrane potential (TMP) induced during the treatment of biological cells with pulsed electric fields have been reported. From the simple analytical models to more complex numerical models requiring significant computational resources, a gamut of methods have been used to recapitu...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2016.10.005

    authors: Murovec T,Sweeney DC,Latouche E,Davalos RV,Brosseau C

    更新日期:2016-11-15 00:00:00

  • Exploring the structure of the 100 amino-acid residue long N-terminus of the plant antenna protein CP29.

    abstract::The structure of the unusually long (∼100 amino-acid residues) N-terminal domain of the light-harvesting protein CP29 of plants is not defined in the crystal structure of this membrane protein. We studied the N-terminus using two electron paramagnetic resonance (EPR) approaches: the rotational diffusion of spin labels...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2013.11.4506

    authors: Shabestari MH,Wolfs CJ,Spruijt RB,van Amerongen H,Huber M

    更新日期:2014-03-18 00:00:00

  • Diffusion-controlled bimolecular reaction rates. The effect of rotational diffusion and orientation constraints.

    abstract::A new approach to the calculation of bimolecular association constants for partially diffusion-limited reactions between asymmetric species (e.g. the ligand binding site of a macromolecule covers only a portion of its surface) is presented. The usual formulation, which is almost always analytically intractable, is bas...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(81)84759-5

    authors: Shoup D,Lipari G,Szabo A

    更新日期:1981-12-01 00:00:00

  • Cargo transport at microtubule crossings: evidence for prolonged tug-of-war between kinesin motors.

    abstract::Intracellular transport of cargos along microtubules is often complicated by the topology of the underlying filament network. The fundamental building blocks for this complex arrangement are filament intersections. The navigation of cargos across microtubule intersections remains poorly understood. Here, we demonstrat...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2015.02.016

    authors: Osunbayo O,Butterfield J,Bergman J,Mershon L,Rodionov V,Vershinin M

    更新日期:2015-03-24 00:00:00

  • Kinetics of ligand binding to receptor immobilized in a polymer matrix, as detected with an evanescent wave biosensor. I. A computer simulation of the influence of mass transport.

    abstract::The influence of mass transport on ligand binding to receptor immobilized in a polymer matrix, as detected with an evanescent wave biosensor, was investigated. A one-dimensional computer model for the mass transport of ligand between the bulk solution and the polymer gel and within the gel was employed, and the influe...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/S0006-3495(96)79681-9

    authors: Schuck P

    更新日期:1996-03-01 00:00:00

  • Understand the Functions of Scaffold Proteins in Cell Signaling by a Mesoscopic Simulation Method.

    abstract::Scaffold proteins are central players in regulating the spatial-temporal organization of many important signaling pathways in cells. They offer physical platforms to downstream signaling proteins so that their transient interactions in a crowded and heterogeneous environment of cytosol can be greatly facilitated. Howe...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/j.bpj.2020.10.002

    authors: Su Z,Dhusia K,Wu Y

    更新日期:2020-11-17 00:00:00

  • Negatively charged residues in the N-terminal of the AID helix confer slow voltage dependent inactivation gating to CaV1.2.

    abstract::The E462R mutation in the fifth position of the AID (alpha1 subunit interaction domain) region in the I-II linker is known to significantly accelerate voltage-dependent inactivation (VDI) kinetics of the L-type CaV1.2 channel, suggesting that the AID region could participate in a hinged-lid type inactivation mechanism...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1529/biophysj.104.045559

    authors: Dafi O,Berrou L,Dodier Y,Raybaud A,Sauvé R,Parent L

    更新日期:2004-11-01 00:00:00

  • Cooperative structural transitions induced by non-homogeneous intramolecular interactions in compact globular proteins.

    abstract::The role played by non-homogeneous interactions in stabilizing cooperative structural changes in proteins was investigated by exhaustive simulations of all compact conformations compatible with several well-defined globule-like shapes in three dimensions. Conformational free energies corresponding to the association o...

    journal_title:Biophysical journal

    pub_type: 杂志文章

    doi:10.1016/s0006-3495(94)80798-2

    authors: Bahar I,Jernigan RL

    更新日期:1994-02-01 00:00:00