Structure of a presenilin family intramembrane aspartate protease.

Abstract:

:Presenilin and signal peptide peptidase (SPP) are intramembrane aspartyl proteases that regulate important biological functions in eukaryotes. Mechanistic understanding of presenilin and SPP has been hampered by lack of relevant structural information. Here we report the crystal structure of a presenilin/SPP homologue (PSH) from the archaeon Methanoculleus marisnigri JR1. The protease, comprising nine transmembrane segments (TMs), adopts a previously unreported protein fold. The amino-terminal domain, consisting of TM1-6, forms a horseshoe-shaped structure, surrounding TM7-9 of the carboxy-terminal domain. The two catalytic aspartate residues are located on the cytoplasmic side of TM6 and TM7, spatially close to each other and approximately 8 Å into the lipid membrane surface. Water molecules gain constant access to the catalytic aspartates through a large cavity between the amino- and carboxy-terminal domains. Structural analysis reveals insights into the presenilin/SPP family of intramembrane proteases.

journal_name

Nature

journal_title

Nature

authors

Li X,Dang S,Yan C,Gong X,Wang J,Shi Y

doi

10.1038/nature11801

subject

Has Abstract

pub_date

2013-01-03 00:00:00

pages

56-61

issue

7430

eissn

0028-0836

issn

1476-4687

pii

nature11801

journal_volume

493

pub_type

杂志文章

相关文献

NATURE文献大全
  • A spin transition mechanism for cooperative adsorption in metal-organic frameworks.

    abstract::Cooperative binding, whereby an initial binding event facilitates the uptake of additional substrate molecules, is common in biological systems such as haemoglobin. It was recently shown that porous solids that exhibit cooperative binding have substantial energetic benefits over traditional adsorbents, but few guideli...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature23674

    authors: Reed DA,Keitz BK,Oktawiec J,Mason JA,Runčevski T,Xiao DJ,Darago LE,Crocellà V,Bordiga S,Long JR

    更新日期:2017-10-05 00:00:00

  • Association between GTPase activators for Rho and Ras families.

    abstract::The ras-related low-molecular-mass GTPases participate in signal transduction involving a variety of cellular functions, including cell-cycle progression, cellular differentiation, cytoskeletal organization, protein transport and secretion. The cycling of these proteins between GTP-bound and GDP-bound states is partia...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/359153a0

    authors: Settleman J,Albright CF,Foster LC,Weinberg RA

    更新日期:1992-09-10 00:00:00

  • Structures of protein-protein complexes involved in electron transfer.

    abstract::Electron transfer reactions are essential for life because they underpin oxidative phosphorylation and photosynthesis, processes leading to the generation of ATP, and are involved in many reactions of intermediary metabolism. Key to these roles is the formation of transient inter-protein electron transfer complexes. T...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature11996

    authors: Antonyuk SV,Han C,Eady RR,Hasnain SS

    更新日期:2013-04-04 00:00:00

  • Identification and processing of proglucagon in pancreatic islets.

    abstract::Immunoprecipitation and tryptic peptide analysis of newly synthesized proteins from rat islets have identified an 18,000 molecular weight (MW) protein as proglucagon. Conversion of this precursor was kinetically similar to the conversion of proinsulin and resulted in the formation of both pancreatic glucagon and a 10,...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/282260a0

    authors: Patzelt C,Tager HS,Carroll RJ,Steiner DF

    更新日期:1979-11-15 00:00:00

  • Chemical and behavioural characterization of the rabbit mammary pheromone.

    abstract::Mammals owe part of their evolutionary success to the harmonious exchanges of information, energy and immunity between females and their offspring. This functional reciprocity is vital for the survival and normal development of infants, and for the inclusive fitness of parents. It is best seen in the intense exchanges...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature01739

    authors: Schaal B,Coureaud G,Langlois D,Giniès C,Sémon E,Perrier G

    更新日期:2003-07-03 00:00:00

  • The genomic signature of dog domestication reveals adaptation to a starch-rich diet.

    abstract::The domestication of dogs was an important episode in the development of human civilization. The precise timing and location of this event is debated and little is known about the genetic changes that accompanied the transformation of ancient wolves into domestic dogs. Here we conduct whole-genome resequencing of dogs...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature11837

    authors: Axelsson E,Ratnakumar A,Arendt ML,Maqbool K,Webster MT,Perloski M,Liberg O,Arnemo JM,Hedhammar A,Lindblad-Toh K

    更新日期:2013-03-21 00:00:00

  • Suppression of insulin feedback enhances the efficacy of PI3K inhibitors.

    abstract::Mutations in PIK3CA, which encodes the p110α subunit of the insulin-activated phosphatidylinositol-3 kinase (PI3K), and loss of function mutations in PTEN, which encodes a phosphatase that degrades the phosphoinositide lipids generated by PI3K, are among the most frequent events in human cancers1,2. However, pharmacol...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-018-0343-4

    authors: Hopkins BD,Pauli C,Du X,Wang DG,Li X,Wu D,Amadiume SC,Goncalves MD,Hodakoski C,Lundquist MR,Bareja R,Ma Y,Harris EM,Sboner A,Beltran H,Rubin MA,Mukherjee S,Cantley LC

    更新日期:2018-08-01 00:00:00

  • Handover mechanism of the growing pilus by the bacterial outer-membrane usher FimD.

    abstract::Pathogenic bacteria such as Escherichia coli assemble surface structures termed pili, or fimbriae, to mediate binding to host-cell receptors1. Type 1 pili are assembled via the conserved chaperone-usher pathway2-5. The outer-membrane usher FimD recruits pilus subunits bound by the chaperone FimC via the periplasmic N-...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-018-0587-z

    authors: Du M,Yuan Z,Yu H,Henderson N,Sarowar S,Zhao G,Werneburg GT,Thanassi DG,Li H

    更新日期:2018-10-01 00:00:00

  • Mechanical induction of the tumorigenic β-catenin pathway by tumour growth pressure.

    abstract::The tumour microenvironment may contribute to tumorigenesis owing to mechanical forces such as fibrotic stiffness or mechanical pressure caused by the expansion of hyper-proliferative cells. Here we explore the contribution of the mechanical pressure exerted by tumour growth onto non-tumorous adjacent epithelium. In t...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature14329

    authors: Fernández-Sánchez ME,Barbier S,Whitehead J,Béalle G,Michel A,Latorre-Ossa H,Rey C,Fouassier L,Claperon A,Brullé L,Girard E,Servant N,Rio-Frio T,Marie H,Lesieur S,Housset C,Gennisson JL,Tanter M,Ménager C,Fre S,Rob

    更新日期:2015-07-02 00:00:00

  • Travel at low energetic cost by swimming and wave-riding bottlenose dolphins.

    abstract::Over the past 50 years there has been much speculation about the energetic cost of swimming and wave-riding by dolphins. When aligned properly in front of the bow of moving ships in the stern wake of small boats, on wind waves, and even in the wake of larger cetaceans, the animals appear to move effortlessly through t...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/355821a0

    authors: Williams TM,Friedl WA,Fong ML,Yamada RM,Sedivy P,Haun JE

    更新日期:1992-02-27 00:00:00

  • Visualizing the generation of memory CD4 T cells in the whole body.

    abstract::It is thought that immunity depends on naive CD4 T cells that proliferate in response to microbial antigens, differentiate into memory cells that produce anti-microbial lymphokines, and migrate to sites of infection. Here we use immunohistology to enumerate individual naive CD4 T cells, specific for a model antigen, i...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35065111

    authors: Reinhardt RL,Khoruts A,Merica R,Zell T,Jenkins MK

    更新日期:2001-03-01 00:00:00

  • Programmed population control by cell-cell communication and regulated killing.

    abstract::De novo engineering of gene circuits inside cells is extremely difficult, and efforts to realize predictable and robust performance must deal with noise in gene expression and variation in phenotypes between cells. Here we demonstrate that by coupling gene expression to cell survival and death using cell-cell communic...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature02491

    authors: You L,Cox RS 3rd,Weiss R,Arnold FH

    更新日期:2004-04-22 00:00:00

  • Keratinocytes blocked in phorbol ester-responsive early stage of terminal differentiation by sarcoma viruses.

    abstract::It has been suggested that the initiation step in mouse skin carcinogenesis involves an alteration in epidermal-differentiation, as mouse basal keratinocytes exposed to initiators resist the arrest of cell growth that is normally associated with the induction of terminal differentiation by calcium ions. The growth of ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/314459a0

    authors: Yuspa SH,Kilkenny AE,Stanley J,Lichti U

    更新日期:1985-04-04 00:00:00

  • Two types of dopamine neuron distinctly convey positive and negative motivational signals.

    abstract::Midbrain dopamine neurons are activated by reward or sensory stimuli predicting reward. These excitatory responses increase as the reward value increases. This response property has led to a hypothesis that dopamine neurons encode value-related signals and are inhibited by aversive events. Here we show that this is tr...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature08028

    authors: Matsumoto M,Hikosaka O

    更新日期:2009-06-11 00:00:00

  • Vaccine protection against Zika virus from Brazil.

    abstract::Zika virus (ZIKV) is a flavivirus that is responsible for the current epidemic in Brazil and the Americas. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans and mice. The rapid development of a safe and effective ZIKV vaccine is a global ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature18952

    authors: Larocca RA,Abbink P,Peron JP,Zanotto PM,Iampietro MJ,Badamchi-Zadeh A,Boyd M,Ng'ang'a D,Kirilova M,Nityanandam R,Mercado NB,Li Z,Moseley ET,Bricault CA,Borducchi EN,Giglio PB,Jetton D,Neubauer G,Nkolola JP,Maxfield

    更新日期:2016-08-25 00:00:00

  • Conformational change and protein-protein interactions of the fusion protein of Semliki Forest virus.

    abstract::Fusion of biological membranes is mediated by specific lipid-interacting proteins that induce the formation and expansion of an initial fusion pore. Here we report the crystal structure of the ectodomain of the Semliki Forest virus fusion glycoprotein E1 in its low-pH-induced trimeric form. E1 adopts a folded-back con...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature02239

    authors: Gibbons DL,Vaney MC,Roussel A,Vigouroux A,Reilly B,Lepault J,Kielian M,Rey FA

    更新日期:2004-01-22 00:00:00

  • Distinct aspects of neuronal differentiation encoded by frequency of spontaneous Ca2+ transients.

    abstract::Stimulation of transient increases in intracellular calcium (Cai2+) activates protein kinases, regulates transcription and influences motility and morphology. Developing neurons generate spontaneous Cai2+ transients, but their role in directing neuronal differentiation and the way in which they encode information are ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/375784a0

    authors: Gu X,Spitzer NC

    更新日期:1995-06-29 00:00:00

  • Exploring biology with small organic molecules.

    abstract::Small organic molecules have proven to be invaluable tools for investigating biological systems, but there is still much to learn from their use. To discover and to use more effectively new chemical tools to understand biology, strategies are needed that allow us to systematically explore 'biological-activity space'. ...

    journal_title:Nature

    pub_type: 杂志文章,评审

    doi:10.1038/nature03196

    authors: Stockwell BR

    更新日期:2004-12-16 00:00:00

  • Martian dust storm impact on atmospheric H2O and D/H observed by ExoMars Trace Gas Orbiter.

    abstract::Global dust storms on Mars are rare1,2 but can affect the Martian atmosphere for several months. They can cause changes in atmospheric dynamics and inflation of the atmosphere3, primarily owing to solar heating of the dust3. In turn, changes in atmospheric dynamics can affect the distribution of atmospheric water vapo...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-019-1097-3

    authors: Vandaele AC,Korablev O,Daerden F,Aoki S,Thomas IR,Altieri F,López-Valverde M,Villanueva G,Liuzzi G,Smith MD,Erwin JT,Trompet L,Fedorova AA,Montmessin F,Trokhimovskiy A,Belyaev DA,Ignatiev NI,Luginin M,Olsen KS,Baggi

    更新日期:2019-04-01 00:00:00

  • Antibody-mediated enhancement of Flavivirus replication in macrophage-like cell lines.

    abstract::Interactions between animal viruses and antiviral antisera may exceptionally result in an apparent increase in viral infectivity. Halstead and coworkers demonstrated enhanced replication of dengue virus (a Flavivirus, family Togaviridae) in human or simian peripheral blood leucocytes carrying Fc receptors at subneutra...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/282509a0

    authors: Peiris JS,Porterfield JS

    更新日期:1979-11-29 00:00:00

  • How 'spin ice' freezes.

    abstract::The large degeneracy of states resulting from the geometrical frustration of competing interactions is an essential ingredient of important problems in fields as diverse as magnetism, protein folding and neural networks. As first explained by Pauling, geometrical frustration of proton positions is also responsible for...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35092516

    authors: Snyder J,Slusky JS,Cava RJ,Schiffer P

    更新日期:2001-09-06 00:00:00

  • Regulated progression of a cultured pre-B-cell line to the B-cell stage.

    abstract::The variable (V) regions of heavy and light immunoglobulin chains are encoded by multiple germline DNA elements which are assembled into complete variable-region genes in precursor(pre-) B lymphocytes. The heavy-chain V region (VH) is assembled from three separate germline DNA elements, the variable (VH), diversity (D...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/317353a0

    authors: Reth MG,Ammirati P,Jackson S,Alt FW

    更新日期:1985-09-26 00:00:00

  • A visual motion detection circuit suggested by Drosophila connectomics.

    abstract::Animal behaviour arises from computations in neuronal circuits, but our understanding of these computations has been frustrated by the lack of detailed synaptic connection maps, or connectomes. For example, despite intensive investigations over half a century, the neuronal implementation of local motion detection in t...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature12450

    authors: Takemura SY,Bharioke A,Lu Z,Nern A,Vitaladevuni S,Rivlin PK,Katz WT,Olbris DJ,Plaza SM,Winston P,Zhao T,Horne JA,Fetter RD,Takemura S,Blazek K,Chang LA,Ogundeyi O,Saunders MA,Shapiro V,Sigmund C,Rubin GM,Scheffe

    更新日期:2013-08-08 00:00:00

  • Calcium signalling in the guidance of nerve growth by netrin-1.

    abstract::Pathfinding by growing axons in the developing nervous system is guided by diffusible or bound factors that attract or repel the axonal growth cone. The cytoplasmic signalling mechanisms that trigger the responses of the growth cone to guidance factors are mostly unknown. Previous studies have shown that the level and...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/47507

    authors: Hong K,Nishiyama M,Henley J,Tessier-Lavigne M,Poo M

    更新日期:2000-01-06 00:00:00

  • Late Tharsis formation and implications for early Mars.

    abstract::The Tharsis region is the largest volcanic complex on Mars and in the Solar System. Young lava flows cover its surface (from the Amazonian period, less than 3 billion years ago) but its growth started during the Noachian era (more than 3.7 billion years ago). Its position has induced a reorientation of the planet with...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature17171

    authors: Bouley S,Baratoux D,Matsuyama I,Forget F,Séjourné A,Turbet M,Costard F

    更新日期:2016-03-17 00:00:00

  • A new family of RhoGEFs activates the Rop molecular switch in plants.

    abstract::In plants, the small GTP-binding proteins called Rops work as signalling switches that control growth, development and plant responses to various environmental stimuli. Rop proteins (Rho of plants, Rac-like and AtRac in Arabidopsis thaliana) belong to the Rho family of Ras-related GTP-binding proteins that turn on sig...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature03883

    authors: Berken A,Thomas C,Wittinghofer A

    更新日期:2005-08-25 00:00:00

  • Structural basis for the final steps of human 40S ribosome maturation.

    abstract::Eukaryotic ribosomes consist of a small 40S and a large 60S subunit that are assembled in a highly coordinated manner. More than 200 factors ensure correct modification, processing and folding of ribosomal RNA and the timely incorporation of ribosomal proteins1,2. Small subunit maturation ends in the cytosol, when the...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-020-2929-x

    authors: Ameismeier M,Zemp I,van den Heuvel J,Thoms M,Berninghausen O,Kutay U,Beckmann R

    更新日期:2020-11-01 00:00:00

  • Syndecan 1 is a critical mediator of macropinocytosis in pancreatic cancer.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) remains recalcitrant to all forms of cancer treatment and carries a five-year survival rate of only 8%1. Inhibition of oncogenic KRAS (hereafter KRAS*), the earliest lesion in disease development that is present in more than 90% of PDACs, and its signalling surrogates has yielde...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-019-1062-1

    authors: Yao W,Rose JL,Wang W,Seth S,Jiang H,Taguchi A,Liu J,Yan L,Kapoor A,Hou P,Chen Z,Wang Q,Nezi L,Xu Z,Yao J,Hu B,Pettazzoni PF,Ho IL,Feng N,Ramamoorthy V,Jiang S,Deng P,Ma GJ,Den P,Tan Z,Zhang SX,Wang H,

    更新日期:2019-04-01 00:00:00

  • Location-level processes drive the establishment of alien bird populations worldwide.

    abstract::Human-mediated translocation of species to areas beyond their natural distribution (which results in 'alien' populations1) is a key signature of the Anthropocene2, and is a primary global driver of biodiversity loss and environmental change3. Stemming the tide of invasions requires understanding why some species fail ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-019-1292-2

    authors: Redding DW,Pigot AL,Dyer EE,Şekercioğlu ÇH,Kark S,Blackburn TM

    更新日期:2019-07-01 00:00:00

  • Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures.

    abstract::Spinocerebellar ataxia type 1 (SCA1) is one of several neurodegenerative disorders caused by an expansion of a polyglutamine tract. It is characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells. To understand the pathogenesis of SCA1, we examined the subcellular localization of ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/40153

    authors: Skinner PJ,Koshy BT,Cummings CJ,Klement IA,Helin K,Servadio A,Zoghbi HY,Orr HT

    更新日期:1997-10-30 00:00:00