Effects of an HIV-1 maturation inhibitor on the structure and dynamics of CA-SP1 junction helices in virus-like particles.

Abstract:

:HIV-1 maturation involves conversion of the immature Gag polyprotein lattice, which lines the inner surface of the viral membrane, to the mature capsid protein (CA) lattice, which encloses the viral RNA. Maturation inhibitors such as bevirimat (BVM) bind within six-helix bundles, formed by a segment that spans the junction between the CA and spacer peptide 1 (SP1) subunits of Gag, and interfere with cleavage between CA and SP1 catalyzed by the HIV-1 protease (PR). We report solid-state NMR (ssNMR) measurements on spherical virus-like particles (VLPs), facilitated by segmental isotopic labeling, that provide information about effects of BVM on the structure and dynamics of CA-SP1 junction helices in the immature lattice. Although BVM strongly blocks PR-catalyzed CA-SP1 cleavage in VLPs and blocks conversion of VLPs to tubular CA assemblies, 15N and 13C ssNMR chemical shifts of segmentally labeled VLPs with and without BVM are very similar, indicating that interaction with BVM does not alter the six-helix bundle structure appreciably. Only the 15N chemical shift of A280 (the first residue of SP1) changes significantly, consistent with BVM binding to an internal ring of hydrophobic side chains of L279 residues. Measurements of transverse 15N spin relaxation rates reveal a reduction in the amplitudes and/or timescales of backbone N-H bond motions, corresponding to a rigidification of the six-helix bundles. Overall, our data show that inhibition of HIV-1 maturation by BVM involves changes in structure and dynamics that are surprisingly subtle, but still sufficient to produce a large effect on CA-SP1 cleavage.

authors

Gupta S,Louis JM,Tycko R

doi

10.1073/pnas.1917755117

subject

Has Abstract

pub_date

2020-05-12 00:00:00

pages

10286-10293

issue

19

eissn

0027-8424

issn

1091-6490

pii

1917755117

journal_volume

117

pub_type

杂志文章
  • Structure of the human villin gene.

    abstract::We have isolated and characterized the complete human villin gene. The villin gene is located on chromosome 2q35-36 in humans and on chromosome 1 in mice. Villin belongs to a family of calcium-regulated actin-binding proteins that share structural and functional homologies. The villin gene is expressed mainly in cells...

    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.88.23.10811

    authors: Pringault E,Robine S,Louvard D

    更新日期:1991-12-01 00:00:00

  • Genomic analysis of human and mouse TCL1 loci reveals a complex of tightly clustered genes.

    abstract::TCL1 and TCL1b genes on human chromosome 14q23.1 are activated in T cell leukemias by translocations and inversions at 14q32.1, juxtaposing them to regulatory elements of T cell receptor genes. In this report we present the cloning, mapping, and expression analysis of the human and murine TCL1/Tcl1 locus. In addition ...

    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.96.25.14418

    authors: Hallas C,Pekarsky Y,Itoyama T,Varnum J,Bichi R,Rothstein JL,Croce CM

    更新日期:1999-12-07 00:00:00

  • Identification of tumor-initiating cells in a highly aggressive brain tumor using promoter activity of nucleostemin.

    abstract::Controversy remains over whether the cancer stem cell (CSC) theory applies to all tumors. To determine whether cells within a highly aggressive solid tumor are stochastically or hierarchically organized, we combined a reporter system where the nucleostemin (NS) promoter drives GFP expression (termed NS-GFP) with a mou...

    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.0905016106

    authors: Tamase A,Muraguchi T,Naka K,Tanaka S,Kinoshita M,Hoshii T,Ohmura M,Shugo H,Ooshio T,Nakada M,Sawamoto K,Onodera M,Matsumoto K,Oshima M,Asano M,Saya H,Okano H,Suda T,Hamada J,Hirao A

    更新日期:2009-10-06 00:00:00

  • Silkworms transformed with chimeric silkworm/spider silk genes spin composite silk fibers with improved mechanical properties.

    abstract::The development of a spider silk-manufacturing process is of great interest. However, there are serious problems with natural manufacturing through spider farming, and standard recombinant protein production platforms have provided limited progress due to their inability to assemble spider silk proteins into fibers. 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.1109420109

    authors: Teulé F,Miao YG,Sohn BH,Kim YS,Hull JJ,Fraser MJ Jr,Lewis RV,Jarvis DL

    更新日期:2012-01-17 00:00:00

  • Induced nucleotide specificity in a GTPase.

    abstract::In signal-recognition particle (SRP)-dependent protein targeting to the bacterial plasma membrane, two GTPases, Ffh (a subunit of the bacterial SRP) and FtsY (the bacterial SRP receptor), act as GTPase activating proteins for one another. The molecular mechanism of this reciprocal GTPase activation is poorly understoo...

    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.0737693100

    authors: Shan SO,Walter P

    更新日期:2003-04-15 00:00:00

  • Structural insights into tail-anchored protein binding and membrane insertion by Get3.

    abstract::Tail-anchored (TA) membrane proteins are involved in a variety of important cellular functions, including membrane fusion, protein translocation, and apoptosis. The ATPase Get3 (Asna1, TRC40) was identified recently as the endoplasmic reticulum targeting factor of TA proteins. Get3 consists of an ATPase and alpha-heli...

    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.0910223106

    authors: Bozkurt G,Stjepanovic G,Vilardi F,Amlacher S,Wild K,Bange G,Favaloro V,Rippe K,Hurt E,Dobberstein B,Sinning I

    更新日期:2009-12-15 00:00:00

  • Identification of a high-affinity binding site involved in the transport of endocannabinoids.

    abstract::Phytocannabinoids, such as the principal bioactive component of marijuana, delta9-tetrahydrocannabinol, have been used for thousands of years for medical and recreational purposes. delta9-Tetrahydrocannabinol and endogenous cannabinoids (e.g., anandamide) initiate their agonist properties by stimulating the cannabinoi...

    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.0507470102

    authors: Moore SA,Nomikos GG,Dickason-Chesterfield AK,Schober DA,Schaus JM,Ying BP,Xu YC,Phebus L,Simmons RM,Li D,Iyengar S,Felder CC

    更新日期:2005-12-06 00:00:00

  • AlgR2 is an ATP/GTP-dependent protein kinase involved in alginate synthesis by Pseudomonas aeruginosa.

    abstract::The exopolysaccharide alginate is a major virulence factor in the pathogenicity of Pseudomonas aeruginosa infecting the lungs of cystic fibrosis (CF) patients. Alginate synthesis by P. aeruginosa is believed to occur in response to environmental signals present in the CF lung. Transcription of a critical alginate bios...

    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.89.7.2659

    authors: Roychoudhury S,Sakai K,Chakrabarty AM

    更新日期:1992-04-01 00:00:00

  • Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry.

    abstract::Electron transfer dissociation (ETD) is a recently introduced mass spectrometric technique that provides a more comprehensive coverage of peptide sequences and posttranslational modifications. Here, we evaluated the use of ETD for a global phosphoproteome analysis. In all, we identified a total of 1,435 phosphorylatio...

    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.0611217104

    authors: Molina H,Horn DM,Tang N,Mathivanan S,Pandey A

    更新日期:2007-02-13 00:00:00

  • "Hidden" sequence periodicities and protein architecture.

    abstract::I demonstrate the existence in protein domain sequences of sets of statistically significant periodic signals, characteristic of the architectures of those domains. It is shown that, although the frequencies of the signals characteristic of a particular architecture have definite wave numbers, they can occur in any ph...

    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.95.15.8580

    authors: Rackovsky S

    更新日期:1998-07-21 00:00:00

  • Dpb11, which interacts with DNA polymerase II(epsilon) in Saccharomyces cerevisiae, has a dual role in S-phase progression and at a cell cycle checkpoint.

    abstract::DPB11, a gene that suppresses mutations in two essential subunits of Saccharomyces cerevisiae DNA polymerase II(epsilon) encoded by POL2 and DPB2, was isolated on a multicopy plasmid. The nucleotide sequence of the DPB11 gene revealed an open reading frame predicting an 87-kDa protein. This protein is homologous to th...

    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.92.25.11791

    authors: Araki H,Leem SH,Phongdara A,Sugino A

    更新日期:1995-12-05 00:00:00

  • Identification of differential translation in genome wide studies.

    abstract::Regulation of gene expression through translational control is a fundamental mechanism implicated in many biological processes ranging from memory formation to innate immunity and whose dysregulation contributes to human diseases. Genome wide analyses of translational control strive to identify differential translatio...

    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.1006821107

    authors: Larsson O,Sonenberg N,Nadon R

    更新日期:2010-12-14 00:00:00

  • Abscisic acid signal transduction in the barley aleurone is mediated by phospholipase D activity.

    abstract::The plant hormones abscisic acid (ABA) and gibberellic acid (GA) are important regulators of the dormancy and germination of seeds. In cereals, GA enhances the synthesis and secretion of enzymes (principally alpha-amylases) in the aleurone cells of the endosperm, which then mobilize the storage reserves that fuel germ...

    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.95.5.2697

    authors: Ritchie S,Gilroy S

    更新日期:1998-03-03 00:00:00

  • A dominant positive and negative selectable gene for use in mammalian cells.

    abstract::We have constructed three different fusion genes containing the herpes simplex virus thymidine kinase (HSV tk) and the bacterial neomycin phosphotransferase (neo) genes. All three fusion genes utilize the HSV tk promoter but differ at the junction of their components. We have determined if the fusion genes are bifunct...

    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.88.23.10416

    authors: Schwartz F,Maeda N,Smithies O,Hickey R,Edelmann W,Skoultchi A,Kucherlapati R

    更新日期:1991-12-01 00:00:00

  • Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus.

    abstract::The generalized seizures of status epilepticus (SE) trigger a series of molecular and cellular events that produce cognitive deficits and can culminate in the development of epilepsy. Known early events include opening of the blood-brain barrier (BBB) and astrocytosis accompanied by activation of brain microglia. Wher...

    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.1604263113

    authors: Varvel NH,Neher JJ,Bosch A,Wang W,Ransohoff RM,Miller RJ,Dingledine R

    更新日期:2016-09-20 00:00:00

  • Glycosylation profiles determine extravasation and disease-targeting properties of armed antibodies.

    abstract::The ability of antibodies to extravasate out of blood vessels is critical for therapeutic activity, because molecular targets for most diseases are located outside of the endothelial lining. By performing detailed biodistribution studies with a novel IL9-armed cancer-specific antibody, we identified a clear correlatio...

    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.1416694112

    authors: Venetz D,Hess C,Lin CW,Aebi M,Neri D

    更新日期:2015-02-17 00:00:00

  • Localization of human factor FVIII inhibitor epitopes to two polypeptide fragments.

    abstract::Epitopes for 22 alloantibodies that inhibit factor VIII procoagulant protein (FVIII) from multitransfused individuals with severe hemophilia A and three autoantibodies from nonhemophilic individuals appeared to be restricted to two specific regions of the FVIII molecule. Immunoblotting of purified FVIII and purified 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.82.22.7728

    authors: Fulcher CA,de Graaf Mahoney S,Roberts JR,Kasper CK,Zimmerman TS

    更新日期:1985-11-01 00:00:00

  • Molecular cloning of the flavin-containing monooxygenase (form II) cDNA from adult human liver.

    abstract::Complementary DNA (cDNA) clones encoding the adult human liver flavin-containing monooxygenase (FMO; dimethylaniline N-oxidase, EC 1.14.13.8) were isolated from lambda gt10 and lambda gt11 libraries. The cDNA libraries were screened with three synthetic 36-mer oligonucleotide probes derived from the nucleic acid seque...

    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.89.5.1685

    authors: Lomri N,Gu Q,Cashman JR

    更新日期:1992-03-01 00:00:00

  • Regional drought-induced reduction in the biomass carbon sink of Canada's boreal forests.

    abstract::The boreal forests, identified as a critical "tipping element" of the Earth's climate system, play a critical role in the global carbon budget. Recent findings have suggested that terrestrial carbon sinks in northern high-latitude regions are weakening, but there has been little observational evidence to support the i...

    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.1111576109

    authors: Ma Z,Peng C,Zhu Q,Chen H,Yu G,Li W,Zhou X,Wang W,Zhang W

    更新日期:2012-02-14 00:00:00

  • Novel human DNA alkyltransferases obtained by random substitution and genetic selection in bacteria.

    abstract::DNA repair alkyltransferases protect organisms against the cytotoxic, mutagenic, and carcinogenic effects of alkylating agents by transferring alkyl adducts from DNA to an active cysteine on the protein, thereby restoring the native DNA structure. We used random sequence substitutions to gain structure-function inform...

    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.93.12.6124

    authors: Christians FC,Loeb LA

    更新日期:1996-06-11 00:00:00

  • Conformational flexibility at the substrate binding site in the lactose permease of Escherichia coli.

    abstract::Glu-126 (helix IV) and Arg-144 (helix V) are charge paired and play a critical role in substrate binding in the lactose permease of Escherichia coli. When Glu-126 is replaced with Asp, the permease has relatively high activity, implying that helix V has sufficient flexibility to allow Arg-144 to accommodate the decrea...

    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.96.20.11178

    authors: Weinglass AB,Kaback HR

    更新日期:1999-09-28 00:00:00

  • The oldest platypus and its bearing on divergence timing of the platypus and echidna clades.

    abstract::Monotremes have left a poor fossil record, and paleontology has been virtually mute during two decades of discussion about molecular clock estimates of the timing of divergence between the platypus and echidna clades. We describe evidence from high-resolution x-ray computed tomography indicating that Teinolophos, an E...

    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.0706385105

    authors: Rowe T,Rich TH,Vickers-Rich P,Springer M,Woodburne MO

    更新日期:2008-01-29 00:00:00

  • Ferredoxin:NADPH oxidoreductase is recruited to thylakoids by binding to a polyproline type II helix in a pH-dependent manner.

    abstract::Ferredoxin:NADPH oxidoreductase (FNR) is a key enzyme of photosynthetic electron transport required for generation of reduction equivalents. Recently, two proteins were found to be involved in membrane-anchoring of FNR by specific interaction via a conserved Ser/Pro-rich motif: Tic62 and Trol. Our crystallographic stu...

    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.1009124107

    authors: Alte F,Stengel A,Benz JP,Petersen E,Soll J,Groll M,Bölter B

    更新日期:2010-11-09 00:00:00

  • Neuronal nonlinearity explains greater visual spatial resolution for darks than lights.

    abstract::Astronomers and physicists noticed centuries ago that visual spatial resolution is higher for dark than light stimuli, but the neuronal mechanisms for this perceptual asymmetry remain unknown. Here we demonstrate that the asymmetry is caused by a neuronal nonlinearity in the early visual pathway. We show that neurons ...

    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.1310442111

    authors: Kremkow J,Jin J,Komban SJ,Wang Y,Lashgari R,Li X,Jansen M,Zaidi Q,Alonso JM

    更新日期:2014-02-25 00:00:00

  • Epac signaling is required for hippocampus-dependent memory retrieval.

    abstract::Previously we uncovered a critical role for norepinephrine and beta(1)-adrenergic signaling in hippocampus-dependent memory retrieval. Because the beta(1) receptor couples to G(s), we examine here whether cAMP is also required for contextual memory retrieval. Using pharmacologic and genetic approaches to manipulate cA...

    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.0804172105

    authors: Ouyang M,Zhang L,Zhu JJ,Schwede F,Thomas SA

    更新日期:2008-08-19 00:00:00

  • Template requirements for the initiation of adenovirus DNA replication.

    abstract::The first step in the replication of the adenovirus genome is the covalent attachment of the 5'-terminal nucleotide, dCMP, to the virus-encoded terminal protein precursor (pTP). This reaction can be observed in vitro and has been previously shown to be dependent upon either viral DNA or linearized plasmid DNA containi...

    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.81.1.100

    authors: Challberg MD,Rawlins DR

    更新日期:1984-01-01 00:00:00

  • Correlation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity with blood-brain barrier monoamine oxidase activity.

    abstract::Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism in humans and subhuman primates, but not in rats and many other laboratory animals; mice are intermediate in their susceptibility. Since MPTP causes selective dopaminergic neurotoxicity when infused directly into rat sub...

    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.84.10.3521

    authors: Kalaria RN,Mitchell MJ,Harik SI

    更新日期:1987-05-01 00:00:00

  • Selective potentiation of Stat-dependent gene expression by collaborator of Stat6 (CoaSt6), a transcriptional cofactor.

    abstract::The molecular mechanisms by which transcription is selectively activated and precisely controlled by signal transducer and activator of transcription (Stat) factors represent a central issue in cytokine-mediated cellular responses. Stat6 mediates responses to IL-4 and antagonizes Stat1 activated by IFN-gamma. We have ...

    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.0506981103

    authors: Goenka S,Boothby M

    更新日期:2006-03-14 00:00:00

  • Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex.

    abstract::Here, using further optimized 3D culture that allows highly selective induction and long-term growth of human ES cell (hESC)-derived cortical neuroepithelium, we demonstrate unique aspects of self-organization in human neocorticogenesis. Self-organized cortical tissue spontaneously forms a polarity along the dorsocaud...

    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.1315710110

    authors: Kadoshima T,Sakaguchi H,Nakano T,Soen M,Ando S,Eiraku M,Sasai Y

    更新日期:2013-12-10 00:00:00

  • Molecular emergence of acute myeloid leukemia during treatment for acute lymphoblastic leukemia.

    abstract::Therapy-related acute myeloid leukemias (t-AML) with translocations of the MLL gene are associated with the use of topoisomerase II inhibitors. We established the emergence of the malignant clone in a child who developed t-AML with a t(11;19) (q23;p13.3) during treatment for acute lymphoblastic leukemia (ALL). The MLL...

    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.181199898

    authors: Blanco JG,Dervieux T,Edick MJ,Mehta PK,Rubnitz JE,Shurtleff S,Raimondi SC,Behm FG,Pui CH,Relling MV

    更新日期:2001-08-28 00:00:00