Noncompetitive Allosteric Antagonism of Death Receptor 5 by a Synthetic Affibody Ligand.

Abstract:

:Fatty acid-induced upregulation of death receptor 5 (DR5) and its cognate ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), promotes hepatocyte lipoapoptosis, which is a key mechanism in the progression of fatty liver disease. Accordingly, inhibition of DR5 signaling represents an attractive strategy for treating fatty liver disease. Ligand competition strategies are prevalent in tumor necrosis factor receptor antagonism, but recent studies have suggested that noncompetitive inhibition through perturbation of the receptor conformation may be a compelling alternative. To this end, we used yeast display and a designed combinatorial library to identify a synthetic 58-amino acid affibody ligand that specifically binds DR5. Biophysical and biochemical studies show that the affibody neither blocks TRAIL binding nor prevents the receptor-receptor interaction. Live-cell fluorescence lifetime measurements indicate that the affibody induces a conformational change in transmembrane dimers of DR5 and favors an inactive state of the receptor. The affibody inhibits apoptosis in TRAIL-treated Huh-7 cells, an in vitro model of fatty liver disease. Thus, this lead affibody serves as a potential drug candidate, with a unique mechanism of action, for fatty liver disease.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Vunnam N,Szymonski S,Hirsova P,Gores GJ,Sachs JN,Hackel BJ

doi

10.1021/acs.biochem.0c00529

subject

Has Abstract

pub_date

2020-10-13 00:00:00

pages

3856-3868

issue

40

eissn

0006-2960

issn

1520-4995

journal_volume

59

pub_type

杂志文章
  • Identification of BECN1 and ATG14 Coiled-Coil Interface Residues That Are Important for Starvation-Induced Autophagy.

    abstract::Autophagy, an essential eukaryotic homeostasis pathway, allows the sequestration of unwanted, damaged, or harmful cytoplasmic components in vesicles called autophagosomes, permitting subsequent lysosomal degradation and nutrient recycling. Autophagosome nucleation is mediated by class III phosphatidylinositol-3-kinase...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.6b00246

    authors: Mei Y,Su M,Sanishvili R,Chakravarthy S,Colbert CL,Sinha SC

    更新日期:2016-08-02 00:00:00

  • Structural Evidence for Dimer-Interface-Driven Regulation of the Type II Cysteine Desulfurase, SufS.

    abstract::SufS is a type II cysteine desulfurase and acts as the initial step in the Suf Fe-S cluster assembly pathway. In Escherichia coli, this pathway is utilized under conditions of oxidative stress and is resistant to reactive oxygen species. Mechanistically, this means SufS must shift between protecting a covalent persulf...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.8b01122

    authors: Dunkle JA,Bruno MR,Outten FW,Frantom PA

    更新日期:2019-02-12 00:00:00

  • Amphitrite ornata dehaloperoxidase (DHP): investigations of structural factors that influence the mechanism of halophenol dehalogenation using "peroxidase-like" myoglobin mutants and "myoglobin-like" DHP mutants.

    abstract::Dehaloperoxidase (DHP), discovered in the marine terebellid polychaete Amphitrite ornata, is the first heme-containing globin with a peroxidase activity. The sequence and crystal structure of DHP argue that it evolved from an ancient O(2) transport and storage globin. Thus, DHP retains an oxygen carrier function but a...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi2009129

    authors: Du J,Huang X,Sun S,Wang C,Lebioda L,Dawson JH

    更新日期:2011-09-27 00:00:00

  • Entrapment of Water at the Transmembrane Helix-Helix Interface of Quiescin Sulfhydryl Oxidase 2.

    abstract::Little is known about how a membrane can regulate interactions between transmembrane helices. Here, we show that strong self-interaction of the transmembrane helix of human quiescin sulfhydryl oxidase 2 rests on a motif of conserved amino acids comprising one face of the helix. Atomistic molecular dynamics simulations...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.5b01239

    authors: Ried CL,Scharnagl C,Langosch D

    更新日期:2016-03-08 00:00:00

  • Interaction with the Redox Cofactor MYW and Functional Role of a Mobile Arginine in Eukaryotic Catalase-Peroxidase.

    abstract::Catalase-peroxidases (KatGs) are unique bifunctional heme peroxidases with an additional posttranslationally formed redox-active Met-Tyr-Trp cofactor that is essential for catalase activity. On the basis of studies of bacterial KatGs, controversial mechanisms of hydrogen peroxide oxidation were proposed. The recent di...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.6b00436

    authors: Gasselhuber B,Graf MM,Jakopitsch C,Zamocky M,Nicolussi A,Furtmüller PG,Oostenbrink C,Carpena X,Obinger C

    更新日期:2016-06-28 00:00:00

  • Measurement of the complexity and diversity of poly(adenylic acid) containing messenger RNA from rat liver.

    abstract::The complexity of rat liver poly (A)+ messenger RNA (mRNA) has been measured by analysis of the kinetics of hydridization with both complementary DNA (cDNA) and single copy DNA. The complementary DNA-poly(A)+ mRNA hybridization reaction demonstrates the existence of three abundance classes representing 18, 37, and 45%...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00596a014

    authors: Savage MJ,Sala-Trepat JM,Bonner J

    更新日期:1978-02-07 00:00:00

  • The conserved residues glutamate-37, aspartate-100, and arginine-269 are important for the structural stabilization of Escherichia coli aspartate transcarbamoylase.

    abstract::Aspartate transcarbamoylase from Escherichia coli is a dodecameric enzyme consisting of two trimeric catalytic subunits and three dimeric regulatory subunits. The X-ray structure of this enzyme indicates that the side chains of His-41, Asp-100, and Asp-90 from one catalytic chain form interactions with the side chains...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00089a034

    authors: Baker DP,Kantrowitz ER

    更新日期:1993-09-28 00:00:00

  • Structure of CuB in the binuclear heme-copper center of the cytochrome aa3-type quinol oxidase from Bacillus subtilis: an ENDOR and EXAFS study.

    abstract::We have studied the structure of the CuB site in the binuclear heme-copper center of the fully oxidized form of the quinol-oxidizing cytochrome aa3-600 from Bacillus subtilis by EXAFS and ENDOR spectroscopy. This enzyme is member of the large superfamily of heme-copper respiratory oxidases, which catalyze the reductio...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00032a019

    authors: Fann YC,Ahmed I,Blackburn NJ,Boswell JS,Verkhovskaya ML,Hoffman BM,Wikström M

    更新日期:1995-08-15 00:00:00

  • Fo membrane domain of ATP synthase from bovine heart mitochondria: purification, subunit composition, and reconstitution with F1-ATPase.

    abstract::The Fo membrane domain of the F1Fo-ATP synthase complex has been purified from bovine heart mitochondria. The purification procedure involves the removal of peripheral membrane proteins, including F1-ATPase, from submitochondrial particles with guanidine hydrochloride, followed by extraction of Fo and other membrane p...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00191a026

    authors: Collinson IR,Runswick MJ,Buchanan SK,Fearnley IM,Skehel JM,van Raaij MJ,Griffiths DE,Walker JE

    更新日期:1994-06-28 00:00:00

  • Combining in Vitro Folding with Cell Free Protein Synthesis for Membrane Protein Expression.

    abstract::Cell free protein synthesis (CFPS) has emerged as a promising methodology for protein expression. While polypeptide production is very reliable and efficient using CFPS, the correct cotranslational folding of membrane proteins during CFPS is still a challenge. In this contribution, we describe a two-step protocol in w...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.6b00488

    authors: Focke PJ,Hein C,Hoffmann B,Matulef K,Bernhard F,Dötsch V,Valiyaveetil FI

    更新日期:2016-08-02 00:00:00

  • Significance of hydrophobic S4-P4 interactions in subtilisin 309 from Bacillus lentus.

    abstract::The subtilisins have an extended substrate binding cleft comprising at least 8 subsites. Two pockets at the S1 and S4 sites are particularly conspicuous, and the interactions between substrate and these two pockets are very important for the substrate specificity. Phe residues have mutationally been introduced at one ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00062a016

    authors: Bech LM,Sørensen SB,Breddam K

    更新日期:1993-03-23 00:00:00

  • cDNA cloning and sequence and cDNA-directed expression of human P450 IIB1: identification of a normal and two variant cDNAs derived from the CYP2B locus on chromosome 19 and differential expression of the IIB mRNAs in human liver.

    abstract::A cDNA designated hIIB1, representing the entire coding sequence of a P450 in the IIB gene family, was isolated from a human liver lambda gt11 library by using the rat IIB1 cDNA as a probe. The hIIB1 protein, deduced from the cDNA sequence, contained 491 amino acids, had a calculated molecular weight of 56,286, and di...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00444a029

    authors: Yamano S,Nhamburo PT,Aoyama T,Meyer UA,Inaba T,Kalow W,Gelboin HV,McBride OW,Gonzalez FJ

    更新日期:1989-09-05 00:00:00

  • Three-state denaturation of DnaK induced by guanidine hydrochloride. Evidence for an expandable intermediate.

    abstract::The denaturation of the heat shock protein DnaK induced by guanidine hydrochloride (Gdn-HCl) was investigated by circular dichroism, fluorescence, size-exclusion HPLC, and dynamic light scattering. DnaK unfolding takes place in two discrete steps. The midpoint (Cm) of the first transition (0.5 M) was shifted to higher...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00067a021

    authors: Palleros DR,Shi L,Reid KL,Fink AL

    更新日期:1993-04-27 00:00:00

  • Posttranslational Chemical Mutagenesis: To Reveal the Role of Noncatalytic Cysteine Residues in Pathogenic Bacterial Phosphatases.

    abstract::The field of chemical site-selective modification of proteins has progressed extensively in recent decades to enable protein functionalization for imaging, drug delivery, and functional studies. In this Perspective, we provide detailed insight into an alternative use of site-selective protein chemistry to probe the ro...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/acs.biochem.8b00639

    authors: Bertoldo JB,Terenzi H,Hüttelmaier S,Bernardes GJL

    更新日期:2018-10-30 00:00:00

  • Conformation-sensitive steroid and fatty acid sites in the transmembrane domain of the nicotinic acetylcholine receptor.

    abstract::The mechanism by which some hydrophobic molecules such as steroids and free fatty acids (FFA) act as noncompetitive inhibitors of the nicotinic acetylcholine receptor (AChR) is still not known. In the present work, we employ Förster resonance energy transfer (FRET) between the intrinsic fluorescence of membrane-bound ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi061388z

    authors: Nievas GA,Barrantes FJ,Antollini SS

    更新日期:2007-03-20 00:00:00

  • Transcription termination factor rho: the site of bicyclomycin inhibition in Escherichia coli.

    abstract::Bicyclomycin is a novel, commercially important antibiotic. Information concerning the site of bicyclomycin inhibition in Escherichia coli has been obtained by the production of bicyclomycin resistant mutants by UV irradiation. Selection by growth in the presence of bicyclomycin of a plasmid clone library generated fr...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00065a007

    authors: Zwiefka A,Kohn H,Widger WR

    更新日期:1993-04-13 00:00:00

  • Targeting of protein phosphatases PP2A and PP2B to the C-terminus of the L-type calcium channel Ca v1.2.

    abstract::The L-type Ca(2+) channel Ca(v)1.2 forms macromolecular signaling complexes that comprise the β(2) adrenergic receptor, trimeric G(s) protein, adenylyl cyclase, and cAMP-dependent protein kinase (PKA) for efficient signaling in heart and brain. The protein phosphatases PP2A and PP2B are part of this complex. PP2A coun...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi101018c

    authors: Xu H,Ginsburg KS,Hall DD,Zimmermann M,Stein IS,Zhang M,Tandan S,Hill JA,Horne MC,Bers D,Hell JW

    更新日期:2010-12-07 00:00:00

  • Rapid reaction kinetics of proline dehydrogenase in the multifunctional proline utilization A protein.

    abstract::The multifunctional proline utilization A (PutA) flavoenzyme from Escherichia coli catalyzes the oxidation of proline to glutamate in two reaction steps using separate proline dehydrogenase (PRODH) and Δ(1)-pyrroline-5-carboxylate (P5C) dehydrogenase domains. Here, the kinetic mechanism of PRODH in PutA is studied by ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi201603f

    authors: Moxley MA,Becker DF

    更新日期:2012-01-10 00:00:00

  • Interaction of myosin subfragments with F-actin.

    abstract::The effect of ionic strength, temperature, and divalent cations on the association of myosin with actin was determined in the ultracentrifuge using scanning absorption optics. The association constant (Ka) for the binding of heavy meromyosin (HmM) to F-actin was 1 X 10(7) M-1 at 20 degrees C, in 0.10 M KCl, 0.01 M imi...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00618a017

    authors: Margossian SS,Lowey S

    更新日期:1978-12-12 00:00:00

  • Homo- and heteronuclear two-dimensional NMR studies of the globular domain of histone H1: full assignment, tertiary structure, and comparison with the globular domain of histone H5.

    abstract::The globular domain of chicken histone H1 (GH1) has been studied by 1H homonuclear and 1H-15N heteronuclear 2D NMR spectroscopy. After the full assignment of the proton and 15N resonances, the tertiary structure of GH1 was determined by an iterative procedure using distance geometry and restrained simulated annealing....

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00203a004

    authors: Cerf C,Lippens G,Ramakrishnan V,Muyldermans S,Segers A,Wyns L,Wodak SJ,Hallenga K

    更新日期:1994-09-20 00:00:00

  • Fidelity of DNA synthesis by the Thermus aquaticus DNA polymerase.

    abstract::We have determined the fidelity of in vitro DNA synthesis catalyzed at high temperature by the DNA polymerase from the thermophilic bacterium Thermus aquaticus. Using a DNA substrate that contains a 3'-OH terminal mismatch, we demonstrate that the purified polymerase lacks detectable exonucleolytic proofreading activi...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00416a027

    authors: Tindall KR,Kunkel TA

    更新日期:1988-08-09 00:00:00

  • Solution structure of the second extracellular loop of human thromboxane A2 receptor.

    abstract::Thromboxane A(2) receptor (TP receptor), a prostanoid receptor, belongs to the G protein-coupled receptor family, composed of three intracellular loops and three extracellular loops connecting seven transmembrane helices. The highly conserved extracellular domains of the prostanoid receptors were found in the second e...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi001867c

    authors: Ruan KH,So SP,Wu J,Li D,Huang A,Kung J

    更新日期:2001-01-09 00:00:00

  • Crystal structures of substrate and substrate analog complexes of protocatechuate 3,4-dioxygenase: endogenous Fe3+ ligand displacement in response to substrate binding.

    abstract::Protocatechuate 3,4-dioxygenase (3,4-PCD) utilizes a ferric ion to catalyze the aromatic ring cleavage of 3,4-dihydroxybenzoate (PCA) by incorporation of both atoms of dioxygen to yield beta-carboxy-cis, cis-muconate. The crystal structures of the anaerobic 3,4-PCD.PCA complex, aerobic complexes with two heterocyclic ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi970469f

    authors: Orville AM,Lipscomb JD,Ohlendorf DH

    更新日期:1997-08-19 00:00:00

  • Genetic regulation of testosterone 15 alpha-hydroxylase (cytochrome P-450(15)alpha) in renal microsomes of female mice.

    abstract::P-450(15)alpha is a form of cytochrome P-450 purified from liver microsomes of female 129/J mice that is specific for oxidation of testosterone to its 15 alpha-hydroxylated product. Testosterone 15 alpha-hydroxylase activity that was inhibited by anti-P-450(15)alpha antibody was approximately 50 times higher in renal ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00365a028

    authors: Squires EJ,Negishi M

    更新日期:1986-08-26 00:00:00

  • Kinetic analysis of product inhibition in human manganese superoxide dismutase.

    abstract::Manganese superoxide dismutase (MnSOD) cycles between the Mn(II) and Mn(III) states during the catalyzed disproportionation of O(2)(*-), a catalysis that is limited at micromolar levels of superoxide by a peroxide-inhibited complex with the metal. We have investigated the role in catalysis and inhibition of the conser...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi011047f

    authors: Hearn AS,Stroupe ME,Cabelli DE,Lepock JR,Tainer JA,Nick HS,Silverman DN

    更新日期:2001-10-09 00:00:00

  • Interactions of wild-type and mutant M protein of vesicular stomatitis virus with viral nucleocapsid and envelope in intact virions. Evidence from [125I]iodonaphthyl azide labeling and specific cross-linking.

    abstract::Four different temperature-sensitive M protein mutants (tsM) of vesicular stomatitis virus (VSV) were characterized with regard to the association of the mutated M protein either with nucleocapsids or with membranes in the intact virions. Virions were labeled with the photoreactive hydrophobic probe [125I]iodonaphthyl...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00527a020

    authors: Mancarella DA,Lenard J

    更新日期:1981-11-24 00:00:00

  • Identification of essential tyrosine and lysine residues in angiotensin converting enzyme: evidence for a single active site.

    abstract::Inactivation of rabbit lung angiotensin converting enzyme (ACE) by 1-fluoro-2,4-dinitrobenzene (Dnp-F) has been shown to be due primarily to the modification of a tyrosine residue [Bünning, P., Kleeman, S.G., & Riordan, J.F. (1990) Biochemistry (preceding paper in this issue)]. Rabbit testicular ACE is also inactivate...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi00498a011

    authors: Chen YN,Riordan JF

    更新日期:1990-11-20 00:00:00

  • Lipid products of phosphoinositide 3-kinase bind human profilin with high affinity.

    abstract::To gain insight into the physiological function of phosphoinositide 3-kinase (PI 3-kinase) lipid products, this study examines the interactions of the D-3 phosphoinositides with profilin and the consequent effects on actin dynamics and phosphoinositide turnover. Profilin, a ubiquitous actin-regulating protein, plays a...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi961878z

    authors: Lu PJ,Shieh WR,Rhee SG,Yin HL,Chen CS

    更新日期:1996-11-05 00:00:00

  • Influence of base stacking and hydrogen bonding on the fluorescence of 2-aminopurine and pyrrolocytosine in nucleic acids.

    abstract::Fluorescent nucleobase analogues are used extensively to probe the structure and dynamics of nucleic acids. The fluorescence of the adenine analogue 2-aminopurine and the cytosine analogue pyrrolocytosine is significantly quenched when the bases are located in regions of double-stranded nucleic acids. To allow more de...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi060479t

    authors: Hardman SJ,Thompson KC

    更新日期:2006-08-01 00:00:00

  • Influence of substrate modification and C-terminal truncation on the active site structure of substrate-bound heme oxygenase from Neisseriae meningitidis. A 1H NMR study.

    abstract::Heme oxygenase (HO), from the pathogenic bacterium N. meningitidis(NmHO), which secures host iron, shares many properties with mammalian HOs but also exhibits some key differences. The crystal structure appears more compact, and the crystal-undetected C-terminus interacts with substrate in solution. The unique nature ...

    journal_title:Biochemistry

    pub_type: 杂志文章

    doi:10.1021/bi200978g

    authors: Peng D,Satterlee JD,Ma LH,Dallas JL,Smith KM,Zhang X,Sato M,La Mar GN

    更新日期:2011-10-18 00:00:00