Probing the Huntingtin 1-17 membrane anchor on a phospholipid bilayer by using all-atom simulations.


:Mislocalization and aggregation of the huntingtin protein are related to Huntington's disease. Its first exon-more specifically the first 17 amino acids (Htt17)-is crucial for the physiological and pathological functions of huntingtin. It regulates huntingtin's activity through posttranslational modifications and serves as an anchor to membrane-containing organelles of the cell. Recently, structure and orientation of the Htt17 membrane anchor were determined using a combined solution and solid-state NMR approach. This prompted us to refine this model by investigating the dynamics and thermodynamics of this membrane anchor on a POPC bilayer using all-atom, explicit solvent molecular dynamics and Hamiltonian replica exchange. Our simulations are combined with various experimental measurements to generate a high-resolution atomistic model for the huntingtin Htt17 membrane anchor on a POPC bilayer. More precisely, we observe that the single α-helix structure is more stable in the phospholipid membrane than the NMR model obtained in the presence of dodecylphosphocholine detergent micelles. The resulting Htt17 monomer has its hydrophobic plane oriented parallel to the bilayer surface. Our results further unveil the key residues interacting with the membrane in terms of hydrogen bonds, salt-bridges, and nonpolar contributions. We also observe that Htt17 equilibrates at a well-defined insertion depth and that it perturbs the physical properties-order parameter, thickness, and area per lipid-of the bilayer in a manner that could favor its dimerization. Overall, our observations reinforce and refine the NMR measurements on the Htt17 membrane anchor segment of huntingtin that is of fundamental importance to its biological functions.


Biophys J


Biophysical journal


Côté S,Binette V,Salnikov ES,Bechinger B,Mousseau N




Has Abstract


2015-03-10 00:00:00














  • Neutron reflectometry studies define prion protein N-terminal peptide membrane binding.

    abstract::The prion protein (PrP), widely recognized to misfold into the causative agent of the transmissible spongiform encephalopathies, has previously been shown to bind to lipid membranes with binding influenced by both membrane composition and pH. Aside from the misfolding events associated with prion pathogenesis, PrP can...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Le Brun AP,Haigh CL,Drew SC,James M,Boland MP,Collins SJ

    更新日期:2014-11-18 00:00:00

  • The role of F-actin and myosin in epithelial cell rheology.

    abstract::Although actin and myosin are important contributors to cell-force generation, shape change, and motility, their contributions to cell stiffness and frequency-dependent rheology have not been conclusively determined. We apply several pharmacological interventions to cultured epithelial cells to elucidate the roles of ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Van Citters KM,Hoffman BD,Massiera G,Crocker JC

    更新日期:2006-11-15 00:00:00

  • Calcium transients and the effect of a photolytically released calcium chelator during electrically induced contractions in rabbit rectococcygeus smooth muscle.

    abstract::Intracellular Ca2+ was determined with the fura-2 technique during electrically induced contractions in the rabbit rectococcygeus smooth muscle at 22 degreesC. The muscles were electrically activated to give short, reproducible contractions. Intracellular [Ca2+] increased during activation; the increase in [Ca2+] prec...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Arner A,Malmqvist U,Rigler R

    更新日期:1998-10-01 00:00:00

  • Origin of axon membrane hyperpolarization under sucrose-gap.

    abstract::One of the disadvantages of the sucrose-gap method for measuring membrane potentials with extracellular electrodes is a membrane hyperpolarization of the order of 30 to 60 mv, as compared with the resting potential obtained with intracellular microelectrodes in the absence of a sucrose-gap. In the present study the co...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Blaustein MP,Goldman DE

    更新日期:1966-07-01 00:00:00

  • Ca2+ and Myosin Cycle States Work as Allosteric Effectors of Troponin Activation.

    abstract::In cardiac muscle, troponin (Tn) and tropomyosin inhibit actin and myosin interactions through the steric blocking of myosin binding to F-actin. Ca2+ binding to Tn C modulates this inhibition. Thin filaments become activated upon Ca2+ binding, which enables strong binding of myosin with a concomitant release of ATP hy...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Solís C,Kim GH,Moutsoglou ME,Robinson JM

    更新日期:2018-11-06 00:00:00

  • Conformation of reconstituted mononucleosomes and effect of linker histone H1 binding studied by scanning force microscopy.

    abstract::The conformation of mononucleosome complexes reconstituted with recombinant core histones on a 614-basepair-long DNA fragment containing the Xenopus borealis 5S rRNA nucleosome positioning sequence was studied by scanning/atomic force microscopy in the absence or presence of linker histone H1. Imaging without prior fi...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Kepert JF,Tóth KF,Caudron M,Mücke N,Langowski J,Rippe K

    更新日期:2003-12-01 00:00:00

  • Gating current harmonics. III. Dynamic transients and steady states with intact sodium inactivation gating.

    abstract::Internally perfused squid giant axons with intact sodium inactivation gating were prepared for gating current experiments. Gating current records were obtained in sinusoidally driven dynamic steady states and as dynamic transients as functions of the mean membrane potential and the frequency of the command sinusoid. C...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Fohlmeister JF,Adelman WJ Jr

    更新日期:1986-09-01 00:00:00

  • Whole-embryo modeling of early segmentation in Drosophila identifies robust and fragile expression domains.

    abstract::Segmentation of the Drosophila melanogaster embryo results from the dynamic establishment of spatial mRNA and protein patterns. Here, we exploit recent temporal mRNA and protein expression measurements on the full surface of the blastoderm to calibrate a dynamical model of the gap gene network on the entire embryo cor...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Bieler J,Pozzorini C,Naef F

    更新日期:2011-07-20 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


    authors: Shoup D,Lipari G,Szabo A

    更新日期:1981-12-01 00:00:00

  • Coarse-grained peptide modeling using a systematic multiscale approach.

    abstract::A systematic new approach to derive multiscale coarse-grained (MS-CG) models has been recently developed. The approach employs information from atomistically detailed simulations to derive CG forces and associated effective potentials. In this work, the MS-CG methodology is extended to study two peptides representing ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Zhou J,Thorpe IF,Izvekov S,Voth GA

    更新日期:2007-06-15 00:00:00

  • Just a Flexible Linker? The Structural and Dynamic Properties of CBP-ID4 Revealed by NMR Spectroscopy.

    abstract::Here, we present a structural and dynamic description of CBP-ID4 at atomic resolution. ID4 is the fourth intrinsically disordered linker of CREB-binding protein (CBP). In spite of the largely disordered nature of CBP-ID4, NMR chemical shifts and relaxation measurements show a significant degree of α-helix sampling in ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Piai A,Calçada EO,Tarenzi T,Grande AD,Varadi M,Tompa P,Felli IC,Pierattelli R

    更新日期:2016-01-19 00:00:00

  • Dynamics of DNA ejection from bacteriophage.

    abstract::The ejection of DNA from a bacterial virus (i.e., phage) into its host cell is a biologically important example of the translocation of a macromolecular chain along its length through a membrane. The simplest mechanism for this motion is diffusion, but in the case of phage ejection a significant driving force derives ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Inamdar MM,Gelbart WM,Phillips R

    更新日期:2006-07-15 00:00:00

  • Structural Thermodynamics of myr-Src(2-19) Binding to Phospholipid Membranes.

    abstract::Many proteins are anchored to lipid bilayer membranes through a combination of hydrophobic and electrostatic interactions. In the case of the membrane-bound nonreceptor tyrosine kinase Src from Rous sarcoma virus, these interactions are mediated by an N-terminal myristoyl chain and an adjacent cluster of six basic ami...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Scheidt HA,Klingler J,Huster D,Keller S

    更新日期:2015-08-04 00:00:00

  • Polyphosphoinositide inclusion in artificial lipid bilayer vesicles promotes divalent cation-dependent membrane fusion.

    abstract::Recent studies suggest that phosphoinositide kinases may participate in intracellular trafficking or exocytotic events. Because both of these events ultimately require fusion of biological membranes, the susceptibility of membranes containing polyphosphoinositides (PPIs) to divalent cation-induced fusion was investiga...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Summers SA,Guebert BA,Shanahan MF

    更新日期:1996-12-01 00:00:00

  • A Model for Link Pruning to Establish Correctly Polarized and Oriented Tip Links in Hair Bundles.

    abstract::Tip links are thought to gate the mechanically sensitive transduction channels of hair cells, but how they form during development and regeneration remains mysterious. In particular, it is unclear how tip links are strung between stereocilia so that they are oriented parallel to a single axis; why their polarity is un...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Tompkins N,Spinelli KJ,Choi D,Barr-Gillespie PG

    更新日期:2017-10-17 00:00:00

  • Cy3-DNA stacking interactions strongly depend on the identity of the terminal basepair.

    abstract::We characterized the effect of the first basepair on the conformational dynamics of the fluorescent dye Cy3 attached to the 5' end of double-stranded DNA using gaussian-mixture adaptive umbrella sampling simulations. In the simulations, the sampling of all five dihedral angles along the linker was enhanced, so that bo...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Spiriti J,Binder JK,Levitus M,van der Vaart A

    更新日期:2011-02-16 00:00:00

  • Universality classes in folding times of proteins.

    abstract::Molecular dynamics simulations in simplified models allow one to study the scaling properties of folding times for many proteins together under a controlled setting. We consider three variants of the Go models with different contact potentials and demonstrate scaling described by power laws and no correlation with the...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Cieplak M,Hoang TX

    更新日期:2003-01-01 00:00:00

  • An electron spin resonance study of interactions between phosphatidylcholine and phosphatidylserine in oriented membranes.

    abstract::A detailed electron spin resonance (ESR) study of mixtures of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and phosphatidylserine (POPS) in oriented multilayers in the liquid crystalline phase is reported with the purpose of characterizing the effects of headgroup mixing on the structural and dynamical properties o...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Ge M,Budil DE,Freed JH

    更新日期:1994-05-01 00:00:00

  • Disentangling Viral Membrane Fusion from Receptor Binding Using Synthetic DNA-Lipid Conjugates.

    abstract::Enveloped viruses must bind to a receptor on the host membrane to initiate infection. Membrane fusion is subsequently initiated by a conformational change in the viral fusion protein, triggered by receptor binding, an environmental change, or both. Here, we present a strategy to disentangle the two processes of recept...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Rawle RJ,Boxer SG,Kasson PM

    更新日期:2016-07-12 00:00:00

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


    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Cassim JY

    更新日期:1992-11-01 00:00:00

  • Dissecting the energies that stabilize sickle hemoglobin polymers.

    abstract::Sickle hemoglobin forms long, multistranded polymers that account for the pathophysiology of the disease. The molecules in these polymers make significant contacts along the polymer axis (i.e., axial contacts) as well as making diagonally directed contacts (i.e., lateral contacts). The axial contacts do not engage the...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Wang Y,Ferrone FA

    更新日期:2013-11-05 00:00:00

  • Local Turgor Pressure Reduction via Channel Clustering.

    abstract::The primary drivers of yeast endocytosis are actin polymerization and curvature-generating proteins, such as clathrin and BAR domain proteins. Previous work has indicated that these factors may not be capable of generating the forces necessary to overcome turgor pressure. Thus local reduction of the turgor pressure, v...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Scher-Zagier JK,Carlsson AE

    更新日期:2016-12-20 00:00:00

  • Asymmetric GUVs prepared by MβCD-mediated lipid exchange: an FCS study.

    abstract::We report a simple method to obtain stable asymmetric giant unilamellar vesicles (GUVs). Fluorescence correlation spectroscopy was used to quantitatively characterize vesicle properties. After brain sphingomyelin (bSM) was exchanged into dioleoylphosphatidylcholine (DOPC) GUVs, lateral diffusion in the bSM-containing ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Chiantia S,Schwille P,Klymchenko AS,London E

    更新日期:2011-01-05 00:00:00

  • Multiple channels mediate calcium leakage in the A7r5 smooth muscle-derived cell line.

    abstract::Ca2+ entry under resting conditions may be important for contraction of vascular smooth muscle, but little is known about the mechanisms involved. Ca2+ leakage was studied in the A7r5 smooth muscle-derived cell line by patch-clamp techniques. Two channels that could mediate calcium influx at resting membrane potential...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Obejero-Paz CA,Jones SW,Scarpa A

    更新日期:1998-09-01 00:00:00

  • The potential landscape of genetic circuits imposes the arrow of time in stem cell differentiation.

    abstract::Differentiation from a multipotent stem or progenitor state to a mature cell is an essentially irreversible process. The associated changes in gene expression patterns exhibit time-directionality. This "arrow of time" in the collective change of gene expression across multiple stable gene expression patterns (attracto...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Wang J,Xu L,Wang E,Huang S

    更新日期:2010-07-07 00:00:00

  • Vesicle size distributions measured by flow field-flow fractionation coupled with multiangle light scattering.

    abstract::The separation method, flow field-flow fractionation (flow FFF), is coupled on-line with multiangle laser light scattering (MALLS) for simultaneous measurement of the size and concentration of vesicles eluting continuously from the fractionator. These size and concentration data, gathered as a function of elution time...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Korgel BA,van Zanten JH,Monbouquette HG

    更新日期:1998-06-01 00:00:00

  • Dominant Driving Forces in Human Telomere Quadruplex Binding-Induced Structural Alterations.

    abstract::Recently various pathways of human telomere (ht) DNA folding into G-quadruplexes and of ligand binding to these structures have been proposed. However, the key issue as to the nature of forces driving the folding and recognition processes remains unanswered. In this study, structural changes of 22-mer ht-DNA fragment ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Bončina M,Hamon F,Islam B,Teulade-Fichou MP,Vesnaver G,Haider S,Lah J

    更新日期:2015-06-16 00:00:00

  • The inhibition of bacteriophage DNA injection by dyes bound to the DNA.

    abstract::A delay ( approximately 10 min) in the appearance of intracellular phage is caused by preincubating the infecting phage T4o(1) in proflavine, acridine orange, or ethidium, but not polyamines. No significant delay in attachment is observed. Apparently the presence of the dye is required inside the permeability barrier ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Dusenbery DB,Uretz RB

    更新日期:1972-08-01 00:00:00

  • Discrete sarcomere length distribution in skeletal muscle.

    abstract::We analyzed the microstructure in the first-order laser diffraction line from both resting and tetanically contracting single twitch fibers from frog anterior tibial muscle to see if the distribution of sarcomere lengths is continuous or discrete. Measuring the distance between adjacent microstructural elements lying ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Tameyasu T,Ishide N,Pollack GH

    更新日期:1982-02-01 00:00:00

  • Transport theory for HIV diffusion through in vivo distributions of topical microbicide gels.

    abstract::Topical microbicide products are being developed for the prevention of sexually transmitted infections. These include vaginally-applied gels that deliver anti-HIV molecules. Gels may also provide partial barriers that slow virion diffusion from semen to vulnerable epithelium, increasing the time during which anti-HIV ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Lai BE,Henderson MH,Peters JJ,Walmer DK,Katz DF

    更新日期:2009-11-04 00:00:00