Cholesterol increases kinetic, energetic, and mechanical stability of the human β2-adrenergic receptor.

Abstract:

:The steroid cholesterol is an essential component of eukaryotic membranes, and it functionally modulates membrane proteins, including G protein-coupled receptors. To reveal insight into how cholesterol modulates G protein-coupled receptors, we have used dynamic single-molecule force spectroscopy to quantify the mechanical strength and flexibility, conformational variability, and kinetic and energetic stability of structural segments stabilizing the human β(2)-adrenergic receptor (β(2)AR) in the absence and presence of the cholesterol analog cholesteryl hemisuccinate (CHS). CHS considerably increased the kinetic, energetic, and mechanical stability of almost every structural segment at sufficient magnitude to alter the structure and functional relationship of β(2)AR. One exception was the structural core segment of β(2)AR, which establishes multiple ligand binding sites, and its properties were not significantly influenced by CHS.

authors

Zocher M,Zhang C,Rasmussen SG,Kobilka BK,Müller DJ

doi

10.1073/pnas.1210373109

subject

Has Abstract

pub_date

2012-12-11 00:00:00

pages

E3463-72

issue

50

eissn

0027-8424

issn

1091-6490

pii

1210373109

journal_volume

109

pub_type

杂志文章
  • Rescue of a foreign gene by Sendai virus.

    abstract::A simple protocol for the rescue of a synthetic genome into a paramyxovirus has been developed. First, a synthetic Sendai virus-like RNA, containing the antisense coding region of the chloramphenicol acetyltransferase gene replacing the coding region of the Sendai virus genome, was transcribed from a cDNA. When introd...

    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.88.13.5537

    authors: Park KH,Huang T,Correia FF,Krystal M

    更新日期:1991-07-01 00:00:00

  • Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation.

    abstract::There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development....

    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.0707741104

    authors: Shaw P,Eckstrand K,Sharp W,Blumenthal J,Lerch JP,Greenstein D,Clasen L,Evans A,Giedd J,Rapoport JL

    更新日期:2007-12-04 00:00:00

  • Photochemically induced dynamic nuclear polarization investigation of complex formation of the NH2-terminal DNA-binding domain of lac repressor with poly[d(AT)].

    abstract::The interaction of the NH2-terminal DNA-binding domain of lac repressor with synthetic oligo[d(AT)] was studied by a photo-CIDNP technique (CIDNP is chemically induced dynamic nuclear polarization). Three of the four tyrosines of the NH2-terminal region were found to be accessible to the photosensitive dye. The corres...

    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.77.9.5145

    authors: Buck F,Rüterjans H,Kaptein R,Beyreuther K

    更新日期:1980-09-01 00:00:00

  • An acquired and a native penicillin-binding protein cooperate in building the cell wall of drug-resistant staphylococci.

    abstract::The blanket resistance of methicillin-resistant Staphylococcus aureus to all beta-lactam antibiotics--which had such a devastating impact on chemotherapy of staphylococcal infections--is related to the properties of the key component of this resistance mechanism: the "acquired" penicillin-binding protein (PBP)-2A, whi...

    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.191260798

    authors: Pinho MG,de Lencastre H,Tomasz A

    更新日期:2001-09-11 00:00:00

  • Transcellular degradation of axonal mitochondria.

    abstract::It is generally accepted that healthy cells degrade their own mitochondria. Here, we report that retinal ganglion cell axons of WT mice shed mitochondria at the optic nerve head (ONH), and that these mitochondria are internalized and degraded by adjacent astrocytes. EM demonstrates that mitochondria are shed through f...

    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.1404651111

    authors: Davis CH,Kim KY,Bushong EA,Mills EA,Boassa D,Shih T,Kinebuchi M,Phan S,Zhou Y,Bihlmeyer NA,Nguyen JV,Jin Y,Ellisman MH,Marsh-Armstrong N

    更新日期:2014-07-01 00:00:00

  • Expression profiles of multiple genes in single neurons of Alzheimer's disease.

    abstract::Many changes have been described in the brains of Alzheimer's disease (AD) patients, including loss of neurons and formation of senile plaques and neurofibrillary tangles. The molecular mechanisms underlying these pathologies are unclear. Northern blot, dot-blot, and reverse transcription-coupled PCR analyses have dem...

    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.95.16.9620

    authors: Chow N,Cox C,Callahan LM,Weimer JM,Guo L,Coleman PD

    更新日期:1998-08-04 00:00:00

  • Cytoplasmic cAMP-sensing domain of hyperpolarization-activated cation (HCN) channels uses two structurally distinct mechanisms to regulate voltage gating.

    abstract::Voltage gating of hyperpolarization-activated cation (HCN) channels is potentiated by direct binding of cAMP to a cytoplasmic cAMP-sensing domain (CSD). When unliganded, the CSD inhibits hyperpolarization-dependent opening of the HCN channel gate; cAMP binding relieves this autoinhibition so that opening becomes more ...

    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.1012750108

    authors: Wicks NL,Wong T,Sun J,Madden Z,Young EC

    更新日期:2011-01-11 00:00:00

  • Cell division cycle 6, a mitotic substrate of polo-like kinase 1, regulates chromosomal segregation mediated by cyclin-dependent kinase 1 and separase.

    abstract::Defining the links between cell division and DNA replication is essential for understanding normal cell cycle progression and tumorigenesis. In this report we explore the effect of phosphorylation of cell division cycle 6 (Cdc6), a DNA replication initiation factor, by polo-like kinase 1 (Plk1) on the regulation of ch...

    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.1013557107

    authors: Yim H,Erikson RL

    更新日期:2010-11-16 00:00:00

  • Structure of a mitochondrial cytochrome c conformer competent for peroxidase activity.

    abstract::At the onset of apoptosis, the peroxidation of cardiolipin at the inner mitochondrial membrane by cytochrome c requires an open coordination site on the heme. We report a 1.45-Å resolution structure of yeast iso-1-cytochrome c with the Met80 heme ligand swung out of the heme crevice and replaced by a water molecule. 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.1323828111

    authors: McClelland LJ,Mou TC,Jeakins-Cooley ME,Sprang SR,Bowler BE

    更新日期:2014-05-06 00:00:00

  • Ventromedial prefrontal cortex supports affective future simulation by integrating distributed knowledge.

    abstract::Although the future often seems intangible, we can make it more concrete by imagining prospective events. Here, using functional MRI, we demonstrate a mechanism by which the ventromedial prefrontal cortex supports such episodic simulations, and thereby contributes to affective foresight: This region supports processes...

    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.1419274111

    authors: Benoit RG,Szpunar KK,Schacter DL

    更新日期:2014-11-18 00:00:00

  • Myosin-binding protein C displaces tropomyosin to activate cardiac thin filaments and governs their speed by an independent mechanism.

    abstract::Myosin-binding protein C (MyBP-C) is an accessory protein of striated muscle thick filaments and a modulator of cardiac muscle contraction. Defects in the cardiac isoform, cMyBP-C, cause heart disease. cMyBP-C includes 11 Ig- and fibronectin-like domains and a cMyBP-C-specific motif. In vitro studies show that in addi...

    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.1316001111

    authors: Mun JY,Previs MJ,Yu HY,Gulick J,Tobacman LS,Beck Previs S,Robbins J,Warshaw DM,Craig R

    更新日期:2014-02-11 00:00:00

  • Long-term and homogeneous regulation of the Escherichia coli araBAD promoter by use of a lactose transporter of relaxed specificity.

    abstract::Expression systems based on the Escherichia coli arabinose operon P(BAD) promoter exhibit the all-or-nothing (autocatalytic) induction of expression that was first documented in the lac operon. Under conditions of subsaturating levels of inducer, some of the cells of the population are fully induced, whereas other cel...

    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.122227599

    authors: Morgan-Kiss RM,Wadler C,Cronan JE Jr

    更新日期:2002-05-28 00:00:00

  • The amino acid sensor GCN2 inhibits inflammatory responses to apoptotic cells promoting tolerance and suppressing systemic autoimmunity.

    abstract::Efficient apoptotic cell clearance and induction of immunologic tolerance is a critical mechanism preventing autoimmunity and associated pathology. Our laboratory has reported that apoptotic cells induce tolerance by a mechanism dependent on the tryptophan catabolizing enzyme indoleamine 2,3 dioxygenase 1 (IDO1) in sp...

    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.1504276112

    authors: Ravishankar B,Liu H,Shinde R,Chaudhary K,Xiao W,Bradley J,Koritzinsky M,Madaio MP,McGaha TL

    更新日期:2015-08-25 00:00:00

  • Cooperative enhancement of specificity in a lattice of T cell receptors.

    abstract::Two of the most important models to account for the specificity and sensitivity of the T cell receptor (TCR) are the kinetic proofreading and serial ligation models. However, although kinetic proofreading provides a means for individual TCRs to measure accurately the length of time they are engaged and signal appropri...

    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.101113698

    authors: Chan C,George AJ,Stark J

    更新日期:2001-05-08 00:00:00

  • Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease.

    abstract::Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T(H)2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of T(H)2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in s...

    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.0905063106

    authors: Mattes J,Collison A,Plank M,Phipps S,Foster PS

    更新日期:2009-11-03 00:00:00

  • Drosophila IRBP bZIP heterodimer binds P-element DNA and affects hybrid dysgenesis.

    abstract::In Drosophila, P-element transposition causes mutagenesis and genome instability during hybrid dysgenesis. The P-element 31-bp terminal inverted repeats (TIRs) contain sequences essential for transposase cleavage and have been implicated in DNA repair via protein-DNA interactions with cellular proteins. The identity 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.1613508113

    authors: Francis MJ,Roche S,Cho MJ,Beall E,Min B,Panganiban RP,Rio DC

    更新日期:2016-11-15 00:00:00

  • Molten-globule conformation of Arc repressor monomers determined by high-pressure 1H NMR spectroscopy.

    abstract::The conformation of the pressure-dissociated monomer of Arc repressor was characterized by 1H NMR spectroscopy. The NMR spectra of the monomer under pressure (up to 5.0 kbar; 1 bar = 100 kPa) are typical of a molten globule and they are considerably different from those of the native dimer and thermally denatured mono...

    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.90.5.1776

    authors: Peng X,Jonas J,Silva JL

    更新日期:1993-03-01 00:00:00

  • Universality of citation distributions: toward an objective measure of scientific impact.

    abstract::We study the distributions of citations received by a single publication within several disciplines, spanning broad areas of science. We show that the probability that an article is cited c times has large variations between different disciplines, but all distributions are rescaled on a universal curve when the relati...

    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.0806977105

    authors: Radicchi F,Fortunato S,Castellano C

    更新日期:2008-11-11 00:00:00

  • Requirement of Rac1 in the development of cardiac hypertrophy.

    abstract::The development of cardiac hypertrophy is mediated, in part, by increase in NADPH oxidase activity and myocardial oxidative stress. The Rho GTPase, Rac, regulates NADPH oxidase activity through interaction with gp91(phox) and p67(phox) (in which "phox" is phagocyte oxidase). However, it is not known which Rac isoform ...

    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.0510444103

    authors: Satoh M,Ogita H,Takeshita K,Mukai Y,Kwiatkowski DJ,Liao JK

    更新日期:2006-05-09 00:00:00

  • Giant multilevel cation channels formed by Alzheimer disease amyloid beta-protein [A beta P-(1-40)] in bilayer membranes.

    abstract::We have recently shown that the Alzheimer disease 40-residue amyloid beta-protein [A beta P-(1-40)] can form cation-selective channels when incorporated into planar lipid bilayers by fusion of liposomes containing the peptide. Since A beta P-(1-40) comprises portions of the putative extracellular and membrane-spanning...

    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.90.22.10573

    authors: Arispe N,Pollard HB,Rojas E

    更新日期:1993-11-15 00:00:00

  • Structure and topological symmetry of the glyphosate target 5-enolpyruvylshikimate-3-phosphate synthase: a distinctive protein fold.

    abstract::5-enol-Pyruvylshikimate-3-phosphate synthase (EPSP synthase; phosphoenolpyruvate:3-phosphoshikimate 1-carboxyvinyltransferase, EC 2.5.1.19) is an enzyme on the pathway toward the synthesis of aromatic amino acids in plants, fungi, and bacteria and is the target of the broad-spectrum herbicide glyphosate. The three-dim...

    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.88.11.5046

    authors: Stallings WC,Abdel-Meguid SS,Lim LW,Shieh HS,Dayringer HE,Leimgruber NK,Stegeman RA,Anderson KS,Sikorski JA,Padgette SR,Kishore GM

    更新日期:1991-06-01 00:00:00

  • Agonist-independent activation of acetylcholine receptor channels by protein kinase A phosphorylation.

    abstract::Protein phosphorylation is a ubiquitous and one of the most effective means of regulating protein activity. Receptor phosphorylation is a key event in signal transduction. The question, therefore, that arises is whether this modulatory mechanism might produce functional changes in a membrane receptor in the absence of...

    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.88.22.10213

    authors: Ferrer-Montiel AV,Montal MS,Díaz-Muñoz M,Montal M

    更新日期:1991-11-15 00:00:00

  • Selectivity of ORC binding sites and the relation to replication timing, fragile sites, and deletions in cancers.

    abstract::The origin recognition complex (ORC) binds sites from which DNA replication is initiated. We address ORC binding selectivity in vivo by mapping ∼52,000 ORC2 binding sites throughout the human genome. The ORC binding profile is broader than those of sequence-specific transcription factors, suggesting that ORC is not bo...

    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.1609060113

    authors: Miotto B,Ji Z,Struhl K

    更新日期:2016-08-16 00:00:00

  • Intramolecular energy transfer and molecular conformation.

    abstract::A discussion of the range of applicability of Forster long-range energy transfer in the determination of macromolecular dimensions and conformational dynamics is given. Emphasis is laid on the effect of restrictions in the orientational freedom of donor and acceptor and on the importance of the orientational averaging...

    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.73.2.271

    authors: Dale RE,Eisinger J

    更新日期:1976-02-01 00:00:00

  • Genetic mapping of Rhizobium meliloti.

    abstract::The drug resistance factor RP4, originally isolated in Pseudomonas, was transferred to Rhizobium meliloti. In that strain, RP4 promotes conjugational transfer of chromosomal markers to form haploid recombinants. This mating system has been used to construct a linkage map of R. meliloti. ...

    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.74.5.2076

    authors: Meade HM,Signer ER

    更新日期:1977-05-01 00:00:00

  • Novel electronic nematicity in heavily hole-doped iron pnictide superconductors.

    abstract::Electronic nematicity, a correlated state that spontaneously breaks rotational symmetry, is observed in several layered quantum materials. In contrast to their liquid-crystal counterparts, the nematic director cannot usually point in an arbitrary direction (XY nematics), but is locked by the crystal to discrete direct...

    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.1909172117

    authors: Ishida K,Tsujii M,Hosoi S,Mizukami Y,Ishida S,Iyo A,Eisaki H,Wolf T,Grube K,V Löhneysen H,Fernandes RM,Shibauchi T

    更新日期:2020-03-24 00:00:00

  • Sequence, tissue distribution, and chromosomal localization of mRNA encoding a human glucose transporter-like protein.

    abstract::cDNA clones encoding a glucose transporter-like protein have been isolated from adult human liver and kidney cDNA libraries by cross-hybridization with the human HepG2/erythrocyte glucose transporter cDNA. Analysis of the sequence of this 524-amino acid glucose transporter-like protein indicates that it has 55.5% iden...

    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.85.15.5434

    authors: Fukumoto H,Seino S,Imura H,Seino Y,Eddy RL,Fukushima Y,Byers MG,Shows TB,Bell GI

    更新日期:1988-08-01 00:00:00

  • Spectrum of HERG K+-channel dysfunction in an inherited cardiac arrhythmia.

    abstract::Long QT syndrome (LQT) is an autosomal dominant disorder that can cause sudden death from cardiac arrhythmias. We recently discovered that mutations in HERG, a K+-channel gene, cause chromosome 7-linked LQT. Heterologous expression of HERG in Xenopus oocytes revealed that HERG current was similar to a well-characteriz...

    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.93.5.2208

    authors: Sanguinetti MC,Curran ME,Spector PS,Keating MT

    更新日期:1996-03-05 00:00:00

  • Sequence-independent upstream DNA-alphaCTD interactions strongly stimulate Escherichia coli RNA polymerase-lacUV5 promoter association.

    abstract::The C-terminal domains of the two alpha-subunits (alphaCTD) in Escherichia coli RNA polymerase (RNAP) recognize specific sequences called UP elements in some promoters. These interactions can increase transcription dramatically. Previously, effects of upstream DNA-alphaCTD interactions on transcription were quantified...

    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.0405814102

    authors: Ross W,Gourse RL

    更新日期:2005-01-11 00:00:00

  • Degassing of reduced carbon from planetary basalts.

    abstract::Degassing of planetary interiors through surface volcanism plays an important role in the evolution of planetary bodies and atmospheres. On Earth, carbon dioxide and water are the primary volatile species in magmas. However, little is known about the speciation and degassing of carbon in magmas formed on other planets...

    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.1219266110

    authors: Wetzel DT,Rutherford MJ,Jacobsen SD,Hauri EH,Saal AE

    更新日期:2013-05-14 00:00:00