Structural Basis of Membrane Protein Chaperoning through the Mitochondrial Intermembrane Space.


:The exchange of metabolites between the mitochondrial matrix and the cytosol depends on β-barrel channels in the outer membrane and α-helical carrier proteins in the inner membrane. The essential translocase of the inner membrane (TIM) chaperones escort these proteins through the intermembrane space, but the structural and mechanistic details remain elusive. We have used an integrated structural biology approach to reveal the functional principle of TIM chaperones. Multiple clamp-like binding sites hold the mitochondrial membrane proteins in a translocation-competent elongated form, thus mimicking characteristics of co-translational membrane insertion. The bound preprotein undergoes conformational dynamics within the chaperone binding clefts, pointing to a multitude of dynamic local binding events. Mutations in these binding sites cause cell death or growth defects associated with impairment of carrier and β-barrel protein biogenesis. Our work reveals how a single mitochondrial "transfer-chaperone" system is able to guide α-helical and β-barrel membrane proteins in a "nascent chain-like" conformation through a ribosome-free compartment.






Weinhäupl K,Lindau C,Hessel A,Wang Y,Schütze C,Jores T,Melchionda L,Schönfisch B,Kalbacher H,Bersch B,Rapaport D,Brennich M,Lindorff-Larsen K,Wiedemann N,Schanda P




Has Abstract


2018-11-15 00:00:00
















  • The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes.

    abstract::Fertilized clam embryos synthesize several new cell-cycle-related proteins. The cloned cDNA and derived amino acid sequences of one of these, cyclin A, are presented here. Immunoblots with an anti-cyclin A antibody reveal that cyclin A is undetectable in oocytes, appears within 15 min of fertilization, and is destroye...


    pub_type: 杂志文章


    authors: Swenson KI,Farrell KM,Ruderman JV

    更新日期:1986-12-26 00:00:00

  • Yeast histone genes show dosage compensation.

    abstract::The copy number of yeast histone genes was increased by inserting an extra H2A,H2B gene pair into the haploid genome by the technique of yeast transformation. The presence of this extra gene copy has no detectable effect on cell growth. The steady-state levels of histone H2A,H2B mRNAs are not elevated in transformed s...


    pub_type: 杂志文章


    authors: Osley MA,Hereford LM

    更新日期:1981-05-01 00:00:00

  • NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion.

    abstract::Mucus production by goblet cells of the large intestine serves as a crucial antimicrobial protective mechanism at the interface between the eukaryotic and prokaryotic cells of the mammalian intestinal ecosystem. However, the regulatory pathways involved in goblet cell-induced mucus secretion remain largely unknown. He...


    pub_type: 杂志文章


    authors: Wlodarska M,Thaiss CA,Nowarski R,Henao-Mejia J,Zhang JP,Brown EM,Frankel G,Levy M,Katz MN,Philbrick WM,Elinav E,Finlay BB,Flavell RA

    更新日期:2014-02-27 00:00:00

  • Rethinking differentiation: stem cells, regeneration, and plasticity.

    abstract::Cell differentiation is an essential process for the development, growth, reproduction, and longevity of all multicellular organisms, and its regulation has been the focus of intense investigation for the past four decades. The study of natural and induced stem cells has ushered an age of re-examination of what it mea...


    pub_type: 杂志文章,评审


    authors: Sánchez Alvarado A,Yamanaka S

    更新日期:2014-03-27 00:00:00

  • The interaction of recombination proteins with supercoiled DNA: defining the role of supercoiling in lambda integrative recombination.

    abstract::Lambda integrative recombination depends on supercoiling of the phage attachment site, attP. Using dimethylsulfate protection and indirect end-labeling, the interaction of the recombination proteins Int and IHF with supercoiled and linear attP has been studied. Supercoiling enhances the binding of Int to attP, but not...


    pub_type: 杂志文章


    authors: Richet E,Abcarian P,Nash HA

    更新日期:1986-09-26 00:00:00

  • Identity Noise and Adipogenic Traits Characterize Dermal Fibroblast Aging.

    abstract::During aging, stromal functions are thought to be impaired, but little is known whether this stems from changes of fibroblasts. Using population- and single-cell transcriptomics, as well as long-term lineage tracing, we studied whether murine dermal fibroblasts are altered during physiological aging under different di...


    pub_type: 杂志文章


    authors: Salzer MC,Lafzi A,Berenguer-Llergo A,Youssif C,Castellanos A,Solanas G,Peixoto FO,Stephan-Otto Attolini C,Prats N,Aguilera M,Martín-Caballero J,Heyn H,Benitah SA

    更新日期:2018-11-29 00:00:00

  • Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans.

    abstract::The sulfated glycosaminoglycan, heparin, was found to release 125I-labeled low density lipoprotein (125I-LDL) from its receptor site on the surface of normal human fibroblasts. Measurement of the amount of 125I-LDL released by heparin permitted the resolution of the total cellular uptake of 125I-LDL at 37 degrees C in...


    pub_type: 杂志文章


    authors: Goldstein JL,Basu SK,Brunschede GY,Brown MS

    更新日期:1976-01-01 00:00:00

  • Beyond Molecular Codes: Simple Rules to Wire Complex Brains.

    abstract::Molecular codes, like postal zip codes, are generally considered a robust way to ensure the specificity of neuronal target selection. However, a code capable of unambiguously generating complex neural circuits is difficult to conceive. Here, we re-examine the notion of molecular codes in the light of developmental alg...


    pub_type: 杂志文章,评审


    authors: Hassan BA,Hiesinger PR

    更新日期:2015-10-08 00:00:00

  • DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression.

    abstract::DMC1 is a new meiosis-specific yeast gene. Dmc1 protein is structurally similar to bacterial RecA proteins. dmc1 mutants are defective in reciprocal recombination, accumulate double-strand break (DSB) recombination intermediates, fail to form normal synaptonemal complex (SC), and arrest late in meiotic prophase. dmc1 ...


    pub_type: 杂志文章


    authors: Bishop DK,Park D,Xu L,Kleckner N

    更新日期:1992-05-01 00:00:00

  • Studies on the activity of the X chromosomes in female teratocarcinoma cells in culture.

    abstract::Embryonal carcinoma cells derived from murine teratocarcinomas are able to differentiate into the same variety of tissue types as early embryonic cells. Because embryonal carcinoma cells resemble those of the embryo at a stage before X chromosome inactivation has occurred in females embryonal carcinoma cells containin...


    pub_type: 杂志文章


    authors: McBurney MW,Adamson ED

    更新日期:1976-09-01 00:00:00

  • HIV-1 structural gene expression requires binding of the Rev trans-activator to its RNA target sequence.

    abstract::Expression of human immunodeficiency virus type 1 structural proteins requires both the viral Rev trans-activator and its cis-acting RNA target sequence, the Rev response element (RRE). The RRE has been mapped to a conserved region of the HIV-1 env gene and is predicted to form a complex, highly stable RNA stem-loop s...


    pub_type: 杂志文章


    authors: Malim MH,Tiley LS,McCarn DF,Rusche JR,Hauber J,Cullen BR

    更新日期:1990-02-23 00:00:00

  • Cellular and molecular signatures of muscle regeneration: current concepts and controversies in adult myogenesis.

    abstract::Adult skeletal muscle generates force in a controlled and directed manner through the contraction of highly specialized, postmitotic, multinucleated myofibers. Life-long muscle function relies on maintenance and regeneration of myofibers through a highly regulated process beginning with activation of normally quiescen...


    pub_type: 杂志文章,评审


    authors: Wagers AJ,Conboy IM

    更新日期:2005-09-09 00:00:00

  • A ligand-gated association between cytoplasmic domains of UNC5 and DCC family receptors converts netrin-induced growth cone attraction to repulsion.

    abstract::Netrins are bifunctional: they attract some axons and repel others. Netrin receptors of the Deleted in Colorectal Cancer (DCC) family are implicated in attraction and those of the UNC5 family in repulsion, but genetic evidence also suggests involvement of the DCC protein UNC-40 in some cases of repulsion. To test whet...


    pub_type: 杂志文章


    authors: Hong K,Hinck L,Nishiyama M,Poo MM,Tessier-Lavigne M,Stein E

    更新日期:1999-06-25 00:00:00

  • cDNA cloning of a novel 85 kd protein that has SH2 domains and regulates binding of PI3-kinase to the PDGF beta-receptor.

    abstract::Using immobilized PDGF receptor as an affinity reagent, we purified an 85 kd protein (p85) from cell lysates and we cloned its cDNA. The protein contains an SH3 domain and two SH2 domains that are homologous to domains found in several receptor-associated enzymes. Recombinant p85 overexpressed in mammalian cells inhib...


    pub_type: 杂志文章


    authors: Escobedo JA,Navankasattusas S,Kavanaugh WM,Milfay D,Fried VA,Williams LT

    更新日期:1991-04-05 00:00:00

  • Nup145p is required for nuclear export of mRNA and binds homopolymeric RNA in vitro via a novel conserved motif.

    abstract::An essential yeast protein, Nup145p, is identified via its genetic interaction with the nucleoporin Nsp1p. Nup145p contains GLFG repeats and localizes to nuclear pores. Depletion of Nup145p in vivo leads rapidly to nuclear retention of polyadenylated RNAs and more slowly to cytoplasmic accumulation of a nuclear report...


    pub_type: 杂志文章


    authors: Fabre E,Boelens WC,Wimmer C,Mattaj IW,Hurt EC

    更新日期:1994-07-29 00:00:00

  • New hope for a microRNA therapy for liver cancer.

    abstract::The loss of expression of particular microRNAs can contribute to tumorigenesis. Kota et al. (2009) now explore in a mouse model a promising new approach for the treatment of liver cancer-re-establishing the expression of an miRNA using a viral vector. ...


    pub_type: 评论,杂志文章


    authors: Rossi JJ

    更新日期:2009-06-12 00:00:00

  • Nonhelical, fibronectin-binding basement-membrane collagen from endodermal cell culture.

    abstract::A novel method of affinity chromatography on insolubilized collagen-binding fragments of fibronectin was utilized to isolate a random-coil collagenous protein from culture media of mouse teratocarcinoma-derived endodermal cells. These cells also produced another collagenous protein, which did not bind to fibronectin b...


    pub_type: 杂志文章


    authors: Engvall E,Bell ML,Carlsson RN,Miller EJ,Ruoslahti E

    更新日期:1982-06-01 00:00:00

  • Neuronal subtype specification within a lineage by opposing temporal feed-forward loops.

    abstract::Neural progenitors generate distinct cell types at different stages, but the mechanisms controlling these temporal transitions are poorly understood. In the Drosophila CNS, a cascade of transcription factors, the "temporal gene cascade," has been identified that acts to alter progenitor competence over time. However, ...


    pub_type: 杂志文章


    authors: Baumgardt M,Karlsson D,Terriente J,Díaz-Benjumea FJ,Thor S

    更新日期:2009-11-25 00:00:00

  • A role for hematopoietic stem cells in promoting angiogenesis.

    abstract::Angiogenesis is an important event for embryonic organogenesis as well as for tissue repair in the adult. Here, we show that hematopoietic stem cells (HSCs) play important roles for angiogenesis during embryogenesis. To investigate the role of HSCs in endothelial cell (EC) development, we analyzed AML1-deficient embry...


    pub_type: 杂志文章


    authors: Takakura N,Watanabe T,Suenobu S,Yamada Y,Noda T,Ito Y,Satake M,Suda T

    更新日期:2000-07-21 00:00:00

  • The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site.

    abstract::The Escherichia coli relBE operon encodes a toxin-antitoxin pair, RelE-RelB. RelB can reverse inhibition of protein synthesis by RelE in vivo. We have found that although RelE does not degrade free RNA, it cleaves mRNA in the ribosomal A site with high codon specificity. Among stop codons UAG is cleaved with fast, UAA...


    pub_type: 杂志文章


    authors: Pedersen K,Zavialov AV,Pavlov MY,Elf J,Gerdes K,Ehrenberg M

    更新日期:2003-01-10 00:00:00

  • The Cdk-activating kinase (CAK) from budding yeast.

    abstract::Activation of the cyclin-dependent kinases to promote cell cycle progression requires their association with cyclins as well as phosphorylation of a threonine (residue 161 in human p34cdc2). This phosphorylation is carried out by CAK, the Cdk-activating kinase. We have purified and cloned CAK from S. cerevisiae. Unlik...


    pub_type: 杂志文章


    authors: Kaldis P,Sutton A,Solomon MJ

    更新日期:1996-08-23 00:00:00

  • Derepression of a neuronal inhibitor due to miRNA dysregulation in a schizophrenia-related microdeletion.

    abstract::22q11.2 microdeletions result in specific cognitive deficits and schizophrenia. Analysis of Df(16)A(+/-) mice, which model this microdeletion, revealed abnormalities in the formation of neuronal dendrites and spines, as well as altered brain microRNAs. Here, we show a drastic reduction of miR-185, which resides within...


    pub_type: 杂志文章


    authors: Xu B,Hsu PK,Stark KL,Karayiorgou M,Gogos JA

    更新日期:2013-01-17 00:00:00

  • Initiation of transcription at the bacterial glnAp2 promoter by purified E. coli components is facilitated by enhancers.

    abstract::The initiation of transcription from the nitrogen-regulated promoter glnAp2 requires RNA polymerase containing sigma 54, the transcriptional activator NRI, and the protein kinase NRII, responsible for the conversion of NRI to the active NRI-phosphate. NRI-phosphate does not increase the ability of sigma 54-containing ...


    pub_type: 杂志文章


    authors: Ninfa AJ,Reitzer LJ,Magasanik B

    更新日期:1987-09-25 00:00:00

  • Nucleosomal organization of telomere-specific chromatin in rat.

    abstract::Rat liver interphase chromosomes have telomeres 20-100 kb in length. Micrococcal nuclease digestion of nuclei cleaves telomeres with a uniform 157 bp periodicity, producing soluble particles that sediment in sucrose gradients exactly like oligonucleosomes. The monomeric telomere particles comigrate with nucleosome cor...


    pub_type: 杂志文章


    authors: Makarov VL,Lejnine S,Bedoyan J,Langmore JP

    更新日期:1993-05-21 00:00:00

  • The relationship of IL-4- and IFN gamma-producing T cells studied by lineage ablation of IL-4-producing cells.

    abstract::Subsets of CD4 T cells are defined by the cytokines that they produce; these cytokines determine the effector function of these cells. Cloned CD4 T cells fall into two subsets, producing either interferon-gamma (IFN gamma) or interleukin-4 (IL-4) in combination with other cytokines, and are called Th1 and Th2 cells, r...


    pub_type: 杂志文章


    authors: Kamogawa Y,Minasi LA,Carding SR,Bottomly K,Flavell RA

    更新日期:1993-12-03 00:00:00

  • No-nonsense functions for long noncoding RNAs.

    abstract::The mysterious secrets of long noncoding RNAs, often referred to as the Dark Matter of the genome, are gradually coming to light. Several recent papers dig deep to reveal surprisingly complex and diverse functions of these enigmatic molecules. ...


    pub_type: 杂志文章,评审


    authors: Nagano T,Fraser P

    更新日期:2011-04-15 00:00:00

  • "Cloaking" on Time: A Cover-Up Act by Resident Tissue Macrophages.

    abstract::In this issue of Cell, Uderhardt et al. employed intravital two-photon microscopy to examine tissue-resident macrophage responses to sterile cellular injuries of variable size. They observed that while multi-cell "macrolesions" are characteristically pro-inflammatory, resident macrophages can "cloak" single-cell micro...


    pub_type: 评论,杂志文章


    authors: Blériot C,Ng LG,Ginhoux F

    更新日期:2019-04-18 00:00:00

  • The inhibition by DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) of hnRNA and mRNA production in HeLa cells.

    abstract::5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB; 75 muM) inhibited only 60-75% of nuclear heterogeneous RNA (hnRNA) synthesis in HeLa cells, while the appearance of labeled cytoplasmic poly(A)-containing messenger RNA (mRNA) was reduced by approximately 95%. DRB-sensitive and resistant transcripts spanned the e...


    pub_type: 杂志文章


    authors: Sehgal PB,Darnell JE Jr,Tamm I

    更新日期:1976-11-01 00:00:00

  • Remembering the Past: A New Form of Protein-Based Inheritance.

    abstract::A comprehensive analysis uncovered a set of yeast proteins promoting protein-based inheritance that shares many of the non-Mendelian properties of prions. Lacking any sequence or structural signatures of known prions, these proteins represent a new class of non-amyloid, protein-based epigenetic determinants that can c...


    pub_type: 杂志文章,评审


    authors: Tuite MF

    更新日期:2016-10-06 00:00:00

  • Gene Expression Changes and Community Turnover Differentially Shape the Global Ocean Metatranscriptome.

    abstract::Ocean microbial communities strongly influence the biogeochemistry, food webs, and climate of our planet. Despite recent advances in understanding their taxonomic and genomic compositions, little is known about how their transcriptomes vary globally. Here, we present a dataset of 187 metatranscriptomes and 370 metagen...


    pub_type: 杂志文章


    authors: Salazar G,Paoli L,Alberti A,Huerta-Cepas J,Ruscheweyh HJ,Cuenca M,Field CM,Coelho LP,Cruaud C,Engelen S,Gregory AC,Labadie K,Marec C,Pelletier E,Royo-Llonch M,Roux S,Sánchez P,Uehara H,Zayed AA,Zeller G,Carmichael

    更新日期:2019-11-14 00:00:00