Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein.

Abstract:

:Multiple sclerosis is a chronic disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal loss. The immunopathogenesis of demyelination in multiple sclerosis involves an autoantibody response to myelin oligodendrocyte glycoprotein (MOG), a type I transmembrane protein located at the surface of CNS myelin. Here we present the crystal structures of the extracellular domain of MOG (MOGIgd) at 1.45-A resolution and the complex of MOGIgd with the antigen-binding fragment (Fab) of the MOG-specific demyelinating monoclonal antibody 8-18C5 at 3.0-A resolution. MOGIgd adopts an IgV like fold with the A'GFCC'C" sheet harboring a cavity similar to the one used by the costimulatory molecule B7-2 to bind its ligand CTLA4. The antibody 8-18C5 binds to three loops located at the membrane-distal side of MOG with a surprisingly dominant contribution made by MOG residues 101-108 containing a strained loop that forms the upper edge of the putative ligand binding site. The sequence R101DHSYQEE108 is unique for MOG, whereas large parts of the remaining sequence are conserved in potentially tolerogenic MOG homologues expressed outside the immuno-privileged environment of the CNS. Strikingly, the only sequence identical to DHSYQEE was found in a Chlamydia trachomatis protein of unknown function, raising the possibility that Chlamydia infections may play a role in the MOG-specific autoimmune response in man. Our data provide the structural basis for the development of diagnostic and therapeutic strategies targeting the pathogenic autoantibody response to MOG.

authors

Breithaupt C,Schubart A,Zander H,Skerra A,Huber R,Linington C,Jacob U

doi

10.1073/pnas.1133443100

keywords:

subject

Has Abstract

pub_date

2003-08-05 00:00:00

pages

9446-51

issue

16

eissn

0027-8424

issn

1091-6490

pii

1133443100

journal_volume

100

pub_type

杂志文章
  • Four hundred-million-year-old vesicular arbuscular mycorrhizae.

    abstract::The discovery of arbuscules in Aglaophyton major, an Early Devonian land plant, provides unequivocal evidence that mycorrhizae were established >400 million years ago. Nonseptate hyphac and arbuscules occur in a specialized meristematic region of the cortex that continually provided new cells for fungal infection. Arb...

    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.91.25.11841

    authors: Remy W,Taylor TN,Hass H,Kerp H

    更新日期:1994-12-06 00:00:00

  • Changes in the shapes of leaves and flowers upon overexpression of cytochrome P450 in Arabidopsis.

    abstract::In Arabidopsis, the two-dimensional expansion of leaves is regulated via the polarized elongation of cells. The ROTUNDIFOLIA3 (ROT3) protein, a member of the family of cytochromes P450, is involved in this process and regulates leaf length. Transgenic plants that overexpressed a wild-type ROT3 gene had longer leaves 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.96.16.9433

    authors: Kim GT,Tsukaya H,Saito Y,Uchimiya H

    更新日期:1999-08-03 00:00:00

  • Unveiling causal interactions in complex systems.

    abstract::Throughout time, operational laws and concepts from complex systems have been employed to quantitatively model important aspects and interactions in nature and society. Nevertheless, it remains enigmatic and challenging, yet inspiring, to predict the actual interdependencies that comprise the structure of such systems...

    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.1918269117

    authors: Stavroglou SK,Pantelous AA,Stanley HE,Zuev KM

    更新日期:2020-04-07 00:00:00

  • Exo-endocytosis and closing of the fission pore during endocytosis in single pituitary nerve terminals internally perfused with high calcium concentrations.

    abstract::An increase in free Ca2+ triggers exocytosis in pituitary nerve terminals leading to an increase in membrane area and membrane capacitance. When Ca2+ is increased by step depolarization, an instantaneous capacitance increase during the first 80 ms is followed by a slow increase extending over several seconds. We measu...

    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.91.12.5267

    authors: Rosenboom H,Lindau M

    更新日期:1994-06-07 00:00:00

  • Isolation and identification of a biologically active peptide derived from the CH3 domain of human IgG1.

    abstract::A 24-amino acid residue peptide has been isolated from the Fc region of a human IgG1 myeloma protein. The peptide has associated with it the same ability to induce murine B cells to polyclonally secrete antibody as does the intact Fc fragment. Amino acid composition of the peptide indicates that on a mole/mole basis 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.79.17.5388

    authors: Morgan EL,Hugli TE,Weigle WO

    更新日期:1982-09-01 00:00:00

  • Deoxycytidine kinase and deoxyguanosine kinase of Lactobacillus acidophilus R-26 are colinear products of a single gene.

    abstract::Three of the four deoxynucleoside kinases required for growth of Lactobacillus acidophilus R-26 exist as heterodimeric pairs specific for deoxyadenosine (dAK) and deoxycytidine (dCK) or dAK and deoxyguanosine (dGK). However, only two tandem genes, dak/dgk, are found, and are expressed only as dAK/dGK in transformed Es...

    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.93.25.14385

    authors: Ma N,Ikeda S,Guo S,Fieno A,Park I,Grimme S,Ikeda T,Ives DH

    更新日期:1996-12-10 00:00:00

  • Changes in type of collagen synthesized as clones of chick chondrocytes grow and eventually lose division capacity.

    abstract::Clones of embryonic chick chondrocytes have been isolated and collagen biosynthesis has been followed as the clones grow and eventually lose division capacity. Analysis of collagen type at each successive subculture until the time of cellular senescence has shown that a change in synthesis occurs from the cartilage-sp...

    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.73.5.1674

    authors: Mayne R,Vail MS,Mayne PM,Miller EJ

    更新日期:1976-05-01 00:00:00

  • Vasopressin mRNA localization in nerve cells: characterization of cis-acting elements and trans-acting factors.

    abstract::mRNA localization is a complex pathway. Besides mRNA sorting per se, this process includes aspects of regulated translation. It requires protein factors that interact with defined sequences (or sequence motifs) of the transcript, and the protein/RNA complexes are finally guided along the cytoskeleton to their ultimate...

    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.111146598

    authors: Mohr E,Prakash N,Vieluf K,Fuhrmann C,Buck F,Richter D

    更新日期:2001-06-19 00:00:00

  • Fusion of dipalmitoylphosphatidylcholine vesicle membranes induced by concanavalin A.

    abstract::The temperature dependence of fatty acid spin label resonance spectra and freeze fracture micrographs of sonicated dipalmitoylphosphatidylcholine vesicles in the absence and presence of concanavalin A demonstrate a strong interaction of concanavalin A with these lipid membranes, which results in fusion of the vesicles...

    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.72.11.4409

    authors: van der Bosch J,McConnell M

    更新日期:1975-11-01 00:00:00

  • Nonplanar peptide bonds in proteins are common and conserved but not biased toward active sites.

    abstract::The planarity of peptide bonds is an assumption that underlies decades of theoretical modeling of proteins. Peptide bonds strongly deviating from planarity are considered very rare features of protein structure that occur for functional reasons. Here, empirical analyses of atomic-resolution protein structures reveal 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.1107115108

    authors: Berkholz DS,Driggers CM,Shapovalov MV,Dunbrack RL Jr,Karplus PA

    更新日期:2012-01-10 00:00:00

  • Responses to pup vocalizations in subordinate naked mole-rats are induced by estradiol ingested through coprophagy of queen's feces.

    abstract::Naked mole-rats form eusocial colonies consisting of a single breeding female (the queen), several breeding males, and sexually immature adults (subordinates). Subordinates are cooperative and provide alloparental care by huddling and retrieving pups to the nest. However, the physiological mechanism(s) underlying allo...

    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.1720530115

    authors: Watarai A,Arai N,Miyawaki S,Okano H,Miura K,Mogi K,Kikusui T

    更新日期:2018-09-11 00:00:00

  • Fibulin-4 exerts a dual role in LTBP-4L-mediated matrix assembly and function.

    abstract::Elastogenesis is a hierarchical process by which cells form functional elastic fibers, providing elasticity and the ability to regulate growth factor bioavailability in tissues, including blood vessels, lung, and skin. This process requires accessory proteins, including fibulin-4 and -5, and latent TGF binding protein...

    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.1901048116

    authors: Kumra H,Nelea V,Hakami H,Pagliuzza A,Djokic J,Xu J,Yanagisawa H,Reinhardt DP

    更新日期:2019-10-08 00:00:00

  • Brain-to-brain coupling during handholding is associated with pain reduction.

    abstract::The mechanisms underlying analgesia related to social touch are not clear. While recent research highlights the role of the empathy of the observer to pain relief in the target, the contribution of social interaction to analgesia is unknown. The current study examines brain-to-brain coupling during pain with interpers...

    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.1703643115

    authors: Goldstein P,Weissman-Fogel I,Dumas G,Shamay-Tsoory SG

    更新日期:2018-03-13 00:00:00

  • Ancient helium and tungsten isotopic signatures preserved in mantle domains least modified by crustal recycling.

    abstract::Rare high-3He/4He signatures in ocean island basalts (OIB) erupted at volcanic hotspots derive from deep-seated domains preserved in Earth's interior. Only high-3He/4He OIB exhibit anomalous 182W-an isotopic signature inherited during the earliest history of Earth-supporting an ancient origin of high 3He/4He. However,...

    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.2009663117

    authors: Jackson MG,Blichert-Toft J,Halldórsson SA,Mundl-Petermeier A,Bizimis M,Kurz MD,Price AA,Harðardóttir S,Willhite LN,Breddam K,Becker TW,Fischer RA

    更新日期:2020-12-08 00:00:00

  • Ultrafast nonthermal heating of water initiated by an X-ray Free-Electron Laser.

    abstract::The bright ultrafast pulses of X-ray Free-Electron Lasers allow investigation into the structure of matter under extreme conditions. We have used single pulses to ionize and probe water as it undergoes a phase transition from liquid to plasma. We report changes in the structure of liquid water on a femtosecond time sc...

    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.1711220115

    authors: Beyerlein KR,Jönsson HO,Alonso-Mori R,Aquila A,Bajt S,Barty A,Bean R,Koglin JE,Messerschmidt M,Ragazzon D,Sokaras D,Williams GJ,Hau-Riege S,Boutet S,Chapman HN,Tîmneanu N,Caleman C

    更新日期:2018-05-29 00:00:00

  • Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria.

    abstract::Human tyrosyl-DNA phosphodiesterase (TDP1) hydrolyzes the phosphodiester bond at a DNA 3'-end linked to a tyrosyl moiety and has been implicated in the repair of topoisomerase I (Top1)-DNA covalent complexes. TDP1 can also hydrolyze other 3'-end DNA alterations including 3'-phosphoglycolate and 3'-abasic sites, and ex...

    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.1009814107

    authors: Das BB,Dexheimer TS,Maddali K,Pommier Y

    更新日期:2010-11-16 00:00:00

  • Pathway-specific control of reward learning and its flexibility via selective dopamine receptors in the nucleus accumbens.

    abstract::In the basal ganglia, inputs from the nucleus accumbens (NAc) are transmitted through both direct and indirect pathways and control reward-based learning. In the NAc, dopamine (DA) serves as a key neurotransmitter, modulating these two parallel pathways. This study explored how reward learning and its flexibility are ...

    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.1210797109

    authors: Yawata S,Yamaguchi T,Danjo T,Hikida T,Nakanishi S

    更新日期:2012-07-31 00:00:00

  • Proenkephalin A in bone-derived cells.

    abstract::Enkephalins, a group of small peptides with opiate-like activity, have been defined originally as neuropeptides. Recent reports showed, using in situ hybridization, that the enkephalin-encoding gene, proenkephalin A (pEnkA), is expressed in nondifferentiated cells of diverse mesodermal lineages. The transient expressi...

    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.88.9.3705

    authors: Rosen H,Polakiewicz RD,Benzakine S,Bar-Shavit Z

    更新日期:1991-05-01 00:00:00

  • Soft X-ray tomography of phenotypic switching and the cellular response to antifungal peptoids in Candida albicans.

    abstract::The opportunistic pathogen Candida albicans can undergo phenotypic switching between a benign, unicellular phenotype and an invasive, multicellular form that causes candidiasis. Increasingly, strains of Candida are becoming resistant to antifungal drugs, making the treatment of candidiasis difficult, especially in imm...

    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.0906145106

    authors: Uchida M,McDermott G,Wetzler M,Le Gros MA,Myllys M,Knoechel C,Barron AE,Larabell CA

    更新日期:2009-11-17 00:00:00

  • Structural basis for MTR4-ZCCHC8 interactions that stimulate the MTR4 helicase in the nuclear exosome-targeting complex.

    abstract::The nuclear exosome-targeting (NEXT) complex functions as an RNA exosome cofactor and is involved in surveillance and turnover of aberrant transcripts and noncoding RNAs. NEXT is a ternary complex composed of the RNA-binding protein RBM7, the scaffold zinc-knuckle protein ZCCHC8, and the helicase MTR4. While RNA inter...

    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.1803530115

    authors: Puno MR,Lima CD

    更新日期:2018-06-12 00:00:00

  • Quantitative trait symmetry independent of Hsp90 buffering: distinct modes of genetic canalization and developmental stability.

    abstract::The Hsp90 chaperone buffers development against a wide range of morphological changes in many organisms and in Drosophila masks the effects of hidden genetic variation. Theory predicts that genetic and nongenetic buffering will share common mechanisms. For example, it is argued that Hsp90 genetic buffering evolved sol...

    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.1835613100

    authors: Milton CC,Huynh B,Batterham P,Rutherford SL,Hoffmann AA

    更新日期:2003-11-11 00:00:00

  • The thermal impulse response of Escherichia coli.

    abstract::Swimming Escherichia coli responds to changes in temperature by modifying its motor behavior. Previous studies using populations of cells have shown that E. coli accumulate in spatial thermal gradients, but these experiments did not cleanly separate thermal responses from chemotactic responses. Here we have isolated 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.0709903105

    authors: Paster E,Ryu WS

    更新日期:2008-04-08 00:00:00

  • Evolutionary erosion of yeast sex chromosomes by mating-type switching accidents.

    abstract::We investigate yeast sex chromosome evolution by comparing genome sequences from 16 species in the family Saccharomycetaceae, including data from genera Tetrapisispora, Kazachstania, Naumovozyma, and Torulaspora. We show that although most yeast species contain a mating-type (MAT) locus and silent HML and HMR loci str...

    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.1112808108

    authors: Gordon JL,Armisén D,Proux-Wéra E,ÓhÉigeartaigh SS,Byrne KP,Wolfe KH

    更新日期:2011-12-13 00:00:00

  • Ultraviolet-stimulated DNA synthesis in toluenzied Escherichia coli deficient in DNA polymerase I.

    abstract::Ultraviolet (UV)-stimulated nonconservative DNA synthesis has been observed in E. coli rendered permeable to nucleoside triphosphates by exposure to toluene. This synthesis is detected in toluenized cells in which the background of UV-independent DNA synthesis is reduced by use of dnaB mutants temperature-sensitive fo...

    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.70.1.129

    authors: Masker WE,Hanawalt PC

    更新日期:1973-01-01 00:00:00

  • Soft, curved electrode systems capable of integration on the auricle as a persistent brain-computer interface.

    abstract::Recent advances in electrodes for noninvasive recording of electroencephalograms expand opportunities collecting such data for diagnosis of neurological disorders and brain-computer interfaces. Existing technologies, however, cannot be used effectively in continuous, uninterrupted modes for more than a few days due to...

    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.1424875112

    authors: Norton JJ,Lee DS,Lee JW,Lee W,Kwon O,Won P,Jung SY,Cheng H,Jeong JW,Akce A,Umunna S,Na I,Kwon YH,Wang XQ,Liu Z,Paik U,Huang Y,Bretl T,Yeo WH,Rogers JA

    更新日期:2015-03-31 00:00:00

  • Social interactions, information use, and the evolution of collective migration.

    abstract::Migration of organisms (or cells) is typically an adaptive response to spatiotemporal variation in resources that requires individuals to detect and respond to long-range and noisy environmental gradients. Many organisms, from wildebeest to bacteria, migrate en masse in a process that can involve a vast number of indi...

    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.1006874107

    authors: Guttal V,Couzin ID

    更新日期:2010-09-14 00:00:00

  • Skeletal and dental morphology supports diphyletic origin of baboons and mandrills.

    abstract::Numerous biomolecular studies from the past 20 years have indicated that the large African monkeys Papio, Theropithecus, and Mandrillus have a diphyletic relationship with different species groups of mangabeys. According to the results of these studies, mandrills and drills (Mandrillus) are most closely related to the...

    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.96.3.1157

    authors: Fleagle JG,McGraw WS

    更新日期:1999-02-02 00:00:00

  • Genetic analysis of cell heredity in imaginal discs of Drosophila melanogaster.

    abstract::Somatic crossing-over was used in heterozygous Drosophila melanogaster to effect clonal homozygosity for three mutants (h, Hw, ac). In these mutants, one type of process, chaetae, replaces another type, trichomes, in specific patterns on the adult fly. Heterozygous individuals were irradiated at different larval or pu...

    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.68.9.2222

    authors: Garcia-Bellido A,Merriam JR

    更新日期:1971-09-01 00:00:00

  • Ultraviolet light-induced labeling by noncompetitive blockers of the acetylcholine receptor from Torpedo marmorata.

    abstract::Reversible ligands were attached covalently to membrane-bound acetylcholine receptor from Torpedo marmorata by a method which is generally applicable and does not require the synthesis of specially designed molecules. UV irradiation of the receptor in the presence of [3H]trimethisoquin, [3H]phencyclidine, or [3H]perhy...

    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.78.6.3925

    authors: Oswald R,Changeux JP

    更新日期:1981-06-01 00:00:00

  • Homolog of tocopherol C methyltransferases catalyzes N methylation in anticancer alkaloid biosynthesis.

    abstract::Madagascar periwinkle (Catharanthus roseus) is the sole source of the anticancer drugs vinblastine and vincristine, bisindole alkaloids derived from the dimerization of the terpenoid indole alkaloids vindoline and catharanthine. Full elucidation of the biosynthetic pathways of these compounds is a prerequisite for met...

    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.1009003107

    authors: Liscombe DK,Usera AR,O'Connor SE

    更新日期:2010-11-02 00:00:00