Cryo-EM structure of a human prion fibril with a hydrophobic, protease-resistant core.

Abstract:

:Self-templating assemblies of the human prion protein are clinically associated with transmissible spongiform encephalopathies. Here we present the cryo-EM structure of a denaturant- and protease-resistant fibril formed in vitro spontaneously by a 9.7-kDa unglycosylated fragment of the human prion protein. This human prion fibril contains two protofilaments intertwined with screw symmetry and linked by a tightly packed hydrophobic interface. Each protofilament consists of an extended beta arch formed by residues 106 to 145 of the prion protein, a hydrophobic and highly fibrillogenic disease-associated segment. Such structures of prion polymorphs serve as blueprints on which to evaluate the potential impact of sequence variants on prion disease.

journal_name

Nat Struct Mol Biol

authors

Glynn C,Sawaya MR,Ge P,Gallagher-Jones M,Short CW,Bowman R,Apostol M,Zhou ZH,Eisenberg DS,Rodriguez JA

doi

10.1038/s41594-020-0403-y

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

417-423

issue

5

eissn

1545-9993

issn

1545-9985

pii

10.1038/s41594-020-0403-y

journal_volume

27

pub_type

杂志文章
  • RPRD1A and RPRD1B are human RNA polymerase II C-terminal domain scaffolds for Ser5 dephosphorylation.

    abstract::The RNA polymerase II (RNAPII) C-terminal domain (CTD) heptapeptide repeats (1-YSPTSPS-7) undergo dynamic phosphorylation and dephosphorylation during the transcription cycle to recruit factors that regulate transcription, RNA processing and chromatin modification. We show here that RPRD1A and RPRD1B form homodimers a...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2853

    authors: Ni Z,Xu C,Guo X,Hunter GO,Kuznetsova OV,Tempel W,Marcon E,Zhong G,Guo H,Kuo WW,Li J,Young P,Olsen JB,Wan C,Loppnau P,El Bakkouri M,Senisterra GA,He H,Huang H,Sidhu SS,Emili A,Murphy S,Mosley AL,Arrowsmith CH

    更新日期:2014-08-01 00:00:00

  • The stalk region of dynamin drives the constriction of dynamin tubes.

    abstract::The GTPase dynamin is essential for numerous vesiculation events including clathrin-mediated endocytosis. Upon GTP hydrolysis, dynamin constricts a lipid bilayer. Previously, a three-dimensional structure of mutant dynamin in the constricted state was determined by helical reconstruction methods. We solved the noncons...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb762

    authors: Chen YJ,Zhang P,Egelman EH,Hinshaw JE

    更新日期:2004-06-01 00:00:00

  • Recognition of helical kinks by xeroderma pigmentosum group A protein triggers DNA excision repair.

    abstract::The function of human XPA protein, a key subunit of the nucleotide excision repair pathway, has been examined with site-directed substitutions in its putative DNA-binding cleft. After screening for repair activity in a host-cell reactivation assay, we analyzed mutants by comparing their affinities for different substr...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1061

    authors: Camenisch U,Dip R,Schumacher SB,Schuler B,Naegeli H

    更新日期:2006-03-01 00:00:00

  • Reconstitution of anaphase DNA bridge recognition and disjunction.

    abstract::Faithful chromosome segregation requires that the sister chromatids be disjoined completely. Defective disjunction can lead to the persistence of histone-free threads of DNA known as ultra-fine bridges (UFBs) that connect the separating sister DNA molecules during anaphase. UFBs arise at specific genomic loci and can ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/s41594-018-0123-8

    authors: Sarlós K,Biebricher AS,Bizard AH,Bakx JAM,Ferreté-Bonastre AG,Modesti M,Paramasivam M,Yao Q,Peterman EJG,Wuite GJL,Hickson ID

    更新日期:2018-09-01 00:00:00

  • Genome-wide CTCF distribution in vertebrates defines equivalent sites that aid the identification of disease-associated genes.

    abstract::Many genomic alterations associated with human diseases localize in noncoding regulatory elements located far from the promoters they regulate, making it challenging to link noncoding mutations or risk-associated variants with target genes. The range of action of a given set of enhancers is thought to be defined by in...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2059

    authors: Martin D,Pantoja C,Fernández Miñán A,Valdes-Quezada C,Moltó E,Matesanz F,Bogdanović O,de la Calle-Mustienes E,Domínguez O,Taher L,Furlan-Magaril M,Alcina A,Cañón S,Fedetz M,Blasco MA,Pereira PS,Ovcharenko I,Recillas-Tar

    更新日期:2011-06-01 00:00:00

  • Linkage between dynamics and catalysis in a thermophilic-mesophilic enzyme pair.

    abstract::A fundamental question is how enzymes can accelerate chemical reactions. Catalysis is not only defined by actual chemical steps, but also by enzyme structure and dynamics. To investigate the role of protein dynamics in enzymatic turnover, we measured residue-specific protein dynamics in hyperthermophilic and mesophili...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb821

    authors: Wolf-Watz M,Thai V,Henzler-Wildman K,Hadjipavlou G,Eisenmesser EZ,Kern D

    更新日期:2004-10-01 00:00:00

  • Direct sequencing of Arabidopsis thaliana RNA reveals patterns of cleavage and polyadenylation.

    abstract::It has recently been shown that RNA 3'-end formation plays a more widespread role in controlling gene expression than previously thought. To examine the impact of regulated 3'-end formation genome-wide, we applied direct RNA sequencing to A. thaliana. Here we show the authentic transcriptome in unprecedented detail an...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2345

    authors: Sherstnev A,Duc C,Cole C,Zacharaki V,Hornyik C,Ozsolak F,Milos PM,Barton GJ,Simpson GG

    更新日期:2012-08-01 00:00:00

  • Two-way communications between ubiquitin-like modifiers and DNA.

    abstract::Many aspects of nucleic acid metabolism, such as DNA replication, repair and transcription, are regulated by the post-translational modifiers ubiquitin and SUMO. Not surprisingly, DNA itself plays an integral part in determining the modification of most chromatin-associated targets. Conversely, ubiquitination or SUMOy...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章,评审

    doi:10.1038/nsmb.2805

    authors: Ulrich HD

    更新日期:2014-04-01 00:00:00

  • Structure and mechanism of the Rubisco-assembly chaperone Raf1.

    abstract::Biogenesis of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits, requires assembly chaperones. Here we analyzed the role of Rubisco accumulation factor1 (Raf1), a dimer of ∼40-kDa subunits. We find that Raf1 from Synechococcus elongatus acts downstream of chaperonin-ass...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3062

    authors: Hauser T,Bhat JY,Miličić G,Wendler P,Hartl FU,Bracher A,Hayer-Hartl M

    更新日期:2015-09-01 00:00:00

  • Dynamic enzyme docking to the ribosome coordinates N-terminal processing with polypeptide folding.

    abstract::Newly synthesized polypeptides undergo various cotranslational maturation steps, including N-terminal enzymatic processing, chaperone-assisted folding and membrane targeting, but the spatial and temporal coordination of these steps is unclear. We show that Escherichia coli methionine aminopeptidase (MAP) associates wi...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2615

    authors: Sandikci A,Gloge F,Martinez M,Mayer MP,Wade R,Bukau B,Kramer G

    更新日期:2013-07-01 00:00:00

  • EJC-independent degradation of nonsense immunoglobulin-mu mRNA depends on 3' UTR length.

    abstract::Inconsistent with prevailing models for nonsense-mediated mRNA decay (NMD) in mammals, the mRNA levels of immunoglobulin-mu (Ig-mu) genes with premature termination codons (PTCs) in the penultimate exon are still reduced by NMD when the intron furthest downstream is deleted. As in yeast, this exon junction complex-ind...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1081

    authors: Bühler M,Steiner S,Mohn F,Paillusson A,Mühlemann O

    更新日期:2006-05-01 00:00:00

  • Structure of an aprataxin-DNA complex with insights into AOA1 neurodegenerative disease.

    abstract::DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP-Zn(2+) comple...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2146

    authors: Tumbale P,Appel CD,Kraehenbuehl R,Robertson PD,Williams JS,Krahn J,Ahel I,Williams RS

    更新日期:2011-10-09 00:00:00

  • Cryo-EM structures reveal translocational unfolding in the clostridial binary iota toxin complex.

    abstract::The iota toxin produced by Clostridium perfringens type E is a binary toxin comprising two independent polypeptides: Ia, an ADP-ribosyltransferase, and Ib, which is involved in cell binding and translocation of Ia across the cell membrane. Here we report cryo-EM structures of the translocation channel Ib-pore and its ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/s41594-020-0388-6

    authors: Yamada T,Yoshida T,Kawamoto A,Mitsuoka K,Iwasaki K,Tsuge H

    更新日期:2020-03-01 00:00:00

  • Structural analysis of the interaction between Hsp90 and the tumor suppressor protein p53.

    abstract::In eukaryotes, the essential dimeric molecular chaperone Hsp90 is required for the activation and maturation of specific substrates such as steroid hormone receptors, tyrosine kinases and transcription factors. Hsp90 is involved in the establishment of cancer and has become an attractive target for drug design. Here w...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2114

    authors: Hagn F,Lagleder S,Retzlaff M,Rohrberg J,Demmer O,Richter K,Buchner J,Kessler H

    更新日期:2011-09-04 00:00:00

  • Complex interactions between the DNA-damage response and mammalian telomeres.

    abstract::Natural chromosome ends resemble double-stranded DNA breaks, but they do not activate a damage response in healthy cells. Telomeres therefore have evolved to solve the 'end-protection problem' by inhibiting multiple DNA damage-response pathways. During the past decade, the view of telomeres has progressed from simple ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章,评审

    doi:10.1038/nsmb.3092

    authors: Arnoult N,Karlseder J

    更新日期:2015-11-01 00:00:00

  • Constitutive splicing and economies of scale in gene expression.

    abstract::In eukaryotic cells, many introns are constitutively, rather than alternatively, spliced and therefore do not contribute to isoform diversification. It has remained unclear what functional roles such constitutive splicing provides. To explore this issue, we asked how splicing affects the efficiency with which individu...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/s41594-019-0226-x

    authors: Ding F,Elowitz MB

    更新日期:2019-06-01 00:00:00

  • Structural model for strain-dependent microtubule activation of Mg-ADP release from kinesin.

    abstract::Mg-ADP release is considered to be a crucial process for the regulation and motility of kinesin. To gain insight into the structural basis of this process, we solved the atomic structures of kinesin superfamily protein-1A (KIF1A) during and after Mg(2+) release. On the basis of new structural and mutagenesis data, we ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1487

    authors: Nitta R,Okada Y,Hirokawa N

    更新日期:2008-10-01 00:00:00

  • The stoichiometry of Gag protein in HIV-1.

    abstract::The major structural components of HIV-1 are encoded as a single polyprotein, Gag, which is sufficient for virus particle assembly. Initially, Gag forms an approximately spherical shell underlying the membrane of the immature particle. After proteolytic maturation of Gag, the capsid (CA) domain of Gag reforms into a c...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb785

    authors: Briggs JA,Simon MN,Gross I,Kräusslich HG,Fuller SD,Vogt VM,Johnson MC

    更新日期:2004-07-01 00:00:00

  • Toward high-resolution computational design of the structure and function of helical membrane proteins.

    abstract::The computational design of α-helical membrane proteins is still in its infancy but has already made great progress. De novo design allows stable, specific and active minimal oligomeric systems to be obtained. Computational reengineering can improve the stability and function of naturally occurring membrane proteins. ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3231

    authors: Barth P,Senes A

    更新日期:2016-06-07 00:00:00

  • Identification and evolution of dual-topology membrane proteins.

    abstract::Integral membrane proteins are generally believed to have unique membrane topologies. However, it has been suggested that dual-topology proteins that adopt a mixture of two opposite orientations in the membrane may exist. Here we show that the membrane orientations of five dual-topology candidates identified in Escher...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1057

    authors: Rapp M,Granseth E,Seppälä S,von Heijne G

    更新日期:2006-02-01 00:00:00

  • 7SK-BAF axis controls pervasive transcription at enhancers.

    abstract::RNA functions at enhancers remain mysterious. Here we show that the 7SK small nuclear RNA (snRNA) inhibits enhancer transcription by modulating nucleosome position. 7SK occupies enhancers and super enhancers genome wide in mouse and human cells, and it is required to limit enhancer-RNA initiation and synthesis in a ma...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3176

    authors: Flynn RA,Do BT,Rubin AJ,Calo E,Lee B,Kuchelmeister H,Rale M,Chu C,Kool ET,Wysocka J,Khavari PA,Chang HY

    更新日期:2016-03-01 00:00:00

  • Messenger RNA interactions in the decoding center control the rate of translocation.

    abstract::During protein synthesis, mRNA and tRNAs are iteratively translocated by the ribosome. Precisely what molecular event is rate limiting for translocation is not known. Here we show that disruption of the interactions between the A-site codon and the ribosome accelerates translocation, suggesting that the release of the...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2140

    authors: Khade PK,Joseph S

    更新日期:2011-10-23 00:00:00

  • Methylation of H4 lysines 5, 8 and 12 by yeast Set5 calibrates chromatin stress responses.

    abstract::Methylation of histones is central to chromatin regulation, and thus previously unknown mechanisms regulating genome function can be revealed through the discovery of new histone methyl marks. Here we identify Set5 as the first histone H4 methyltransferase, which monomethylates the critical H4 lysine residues 5, 8 and...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2252

    authors: Green EM,Mas G,Young NL,Garcia BA,Gozani O

    更新日期:2012-02-19 00:00:00

  • Structural mimicry in transcription regulation of human RNA polymerase II by the DNA helicase RECQL5.

    abstract::RECQL5 is a member of the highly conserved RecQ family of DNA helicases involved in DNA repair. RECQL5 interacts with RNA polymerase II (Pol II) and inhibits transcription of protein-encoding genes by an unknown mechanism. We show that RECQL5 contacts the Rpb1 jaw domain of Pol II at a site that overlaps with the bind...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2596

    authors: Kassube SA,Jinek M,Fang J,Tsutakawa S,Nogales E

    更新日期:2013-07-01 00:00:00

  • Architecture of the Saccharomyces cerevisiae RNA polymerase I Core Factor complex.

    abstract::Core Factor (CF) is a conserved RNA polymerase (Pol) I general transcription factor comprising Rrn6, Rrn11 and the TFIIB-related subunit Rrn7. CF binds TATA-binding protein (TBP), Pol I and the regulatory factors Rrn3 and upstream activation factor. We used chemical cross-linking-MS to determine the molecular architec...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2873

    authors: Knutson BA,Luo J,Ranish J,Hahn S

    更新日期:2014-09-01 00:00:00

  • Interaction between the keratin cytoskeleton and eEF1Bgamma affects protein synthesis in epithelial cells.

    abstract::Eukaryotic elongation factor-1 (eEF1) is essential for peptide-chain elongation during translation. We report that its gamma subunit (eEF1Bgamma) specifically binds, and bundles, keratin intermediate filaments. Disrupting this interaction depresses translation by approximately 20% and selectively increases 80S ribosom...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1301

    authors: Kim S,Kellner J,Lee CH,Coulombe PA

    更新日期:2007-10-01 00:00:00

  • BRD4 assists elongation of both coding and enhancer RNAs by interacting with acetylated histones.

    abstract::Small-molecule BET inhibitors interfere with the epigenetic interactions between acetylated histones and the bromodomains of the BET family proteins, including BRD4, and they potently inhibit growth of malignant cells by targeting cancer-promoting genes. BRD4 interacts with the pause-release factor P-TEFb and has been...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2912

    authors: Kanno T,Kanno Y,LeRoy G,Campos E,Sun HW,Brooks SR,Vahedi G,Heightman TD,Garcia BA,Reinberg D,Siebenlist U,O'Shea JJ,Ozato K

    更新日期:2014-12-01 00:00:00

  • Structural basis for the molecular evolution of SRP-GTPase activation by protein.

    abstract::Small G proteins have key roles in signal transduction pathways. They are switched from the signaling 'on' to the non-signaling 'off' state when GTPase-activating proteins (GAPs) provide a catalytic residue. The ancient signal recognition particle (SRP)-type GTPases form GTP-dependent homo- and heterodimers and deviat...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2141

    authors: Bange G,Kümmerer N,Grudnik P,Lindner R,Petzold G,Kressler D,Hurt E,Wild K,Sinning I

    更新日期:2011-11-06 00:00:00

  • Catching DNA with hoops-biophysical approaches to clarify the mechanism of SMC proteins.

    abstract::Structural maintenance of chromosome (SMC) complexes are central regulators of chromosome architecture that are essential in all domains of life. For decades, the structural biology field has been debating how these conserved protein complexes use their intricate ring-like structures to structurally organize DNA. Here...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章,评审

    doi:10.1038/nsmb.3507

    authors: Eeftens J,Dekker C

    更新日期:2017-12-07 00:00:00

  • Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller domain.

    abstract::The structure of the Sortilin ectodomain in complex with neurotensin has been determined at 2-A resolution, revealing that the C-terminal part of neurotensin binds in the tunnel of a ten-bladed beta-propeller domain. Binding competition studies suggest that additional binding sites, for example, for the prodomain of n...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1543

    authors: Quistgaard EM,Madsen P,Grøftehauge MK,Nissen P,Petersen CM,Thirup SS

    更新日期:2009-01-01 00:00:00