Zinc finger mutations that alter domain interactions in the glucocorticoid receptor.

Abstract:

:The DNA binding domain of steroid receptors coincides with the cysteine-rich region encompassing the two conserved zinc fingers. In the case of the glucocorticoid receptor (GR), a weak transactivation function has been described to be adjacent or partly overlapping to the DNA binding domain, whereas stronger trans-acting functions are encoded by the amino and the carboxy domain. In this report we describe the phenotype produced by stochastic mutations of the zinc finger region. The mutants were obtained either by selected rearrangements of the rat GR cDNA, or by semi-random nucleotide substitutions. All the identified permissive rearrangements were confined to a region downstream from the first zinc finger (duplications starting between residue 474 and 492). In general, the phenotype of point mutations is compatible with established structural data. Nevertheless, we found two unexpected phenotypes. First, we noticed that the double mutant His451 Asn/Ser459Gly is stronger than the wild-type sequence in DNA binding. Secondly, substitution of the conserved Lys461 results in an abnormal behavior of the mutated GR. In particular, the mutant Lys461Tyr (61Y) displays about the same transactivation when tested in form of a minimal GR fragment (amino acids 407/556) as when tested in the amino-prolongued GR fragment (amino acids 3-556, which contains the major transactivation domain of the GR). This is in contrast with the behavior of the other mutants in which the residue 461 is intact. In these cases, transactivation capacity is normally increased more than 30-fold from GR407-556 to GR3-556. These results are discussed in terms of possible cross-talk among the DNA binding domain and other functions residing in the amino domain of the GR.

journal_name

J Mol Biol

authors

Zandi E,Galli I,Döbbeling U,Rusconi S

doi

10.1006/jmbi.1993.1130

subject

Has Abstract

pub_date

1993-03-05 00:00:00

pages

124-36

issue

1

eissn

0022-2836

issn

1089-8638

pii

S0022283683711307

journal_volume

230

pub_type

杂志文章
  • Probing a tRNA core that contributes to aminoacylation.

    abstract::The contribution of the tRNA "core" to aminoacylation is beginning to be recognized. One example is the core region of Escherichia coli tRNA(Cys), which has been shown by biochemical studies to be important for aminoacylation. This core has several layers of unusual base-pairs, which are revealed by the recent crystal...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1999.3353

    authors: Hamann CS,Hou YM

    更新日期:2000-01-28 00:00:00

  • Translocation of histone proteins across lipid bilayers and Mycoplasma membranes.

    abstract::We show that the three core histones H2A, H3 and H4 can transverse lipid bilayers of large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs). In contrast, the histone H2B, although able to bind to the liposomes, fails to penetrate the unilamellar and the multilamellar vesicles. Translocation across the lip...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2004.10.046

    authors: Rosenbluh J,Hariton-Gazal E,Dagan A,Rottem S,Graessmann A,Loyter A

    更新日期:2005-01-14 00:00:00

  • A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity.

    abstract::The SH2 domain of the C-terminal Src kinase [Csk] contains a unique disulfide bond that is not present in other known SH2 domains. To investigate whether this unusual disulfide bond serves a novel function, the effects of disulfide bond formation on catalytic activity of the full-length protein and on the structure of...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2006.10.076

    authors: Mills JE,Whitford PC,Shaffer J,Onuchic JN,Adams JA,Jennings PA

    更新日期:2007-02-02 00:00:00

  • Folding of RNA involves parallel pathways.

    abstract::Folding kinetics of large RNAs are just beginning to be investigated. We show that the Tetrahymena self-splicing RNA partitions into a population that rapidly reaches the native state, and a slowly folding population that is trapped in metastable misfolded structures. Transitions from the misfolded structures to the n...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1997.1311

    authors: Pan J,Thirumalai D,Woodson SA

    更新日期:1997-10-17 00:00:00

  • Recognition and cleavage of the bacteriophage P1 packaging site (pac). II. Functional limits of pac and location of pac cleavage termini.

    abstract::Bacteriophage P1 initiates the processive packaging of its DNA at a unique site called pac. We show that a functional pac site is contained within a 161 base-pair segment of P1 EcoRI fragment 20. It extends from a position 71 base-pairs to a position 232 base-pairs from the EcoRI-22 proximal side of that fragment. The...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(87)90675-9

    authors: Sternberg N,Coulby J

    更新日期:1987-04-05 00:00:00

  • Refined crystal structure of the catalytic domain of dihydrolipoyl transacetylase (E2p) from Azotobacter vinelandii at 2.6 A resolution.

    abstract::Dihydrolipoyl transacetylase (E2p) is both structurally and functionally the central enzyme of the pyruvate dehydrogenase multienzyme complex. The crystal structure of the catalytic domain, i.e. residues 382 to 637, of Azotobacter vinelandii E2p (E2pCD) was solved by multiple isomorphous replacement and refined by ene...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1993.1235

    authors: Mattevi A,Obmolova G,Kalk KH,Westphal AH,de Kok A,Hol WG

    更新日期:1993-04-20 00:00:00

  • Structure and specificity of a binary tandem domain F-lectin from striped bass (Morone saxatilis).

    abstract::The plasma of the striped bass Morone saxatilis contains a fucose-specific lectin (MsaFBP32) that consists of two F-type carbohydrate recognition domains (CRDs) in tandem. The crystal structure of the complex of MsaFBP32 with l-fucose reported here shows a cylindrical 81-A-long and 60-A-wide trimer divided into two gl...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2010.06.018

    authors: Bianchet MA,Odom EW,Vasta GR,Amzel LM

    更新日期:2010-08-13 00:00:00

  • Structure of the myosin projections on native thick filaments from vertebrate skeletal muscle.

    abstract::Rabbit psoas muscle filaments, isolated in relaxing buffer from non-glycerinated muscle, have been applied to hydrophilic carbon films and stained with uranyl acetate. Electron micrographs were obtained under low-dose conditions to minimize specimen damage. Surrounding the filament backbone, except in the bare zone, i...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(84)90295-x

    authors: Knight P,Trinick J

    更新日期:1984-08-15 00:00:00

  • Solution structure and dynamics of the wild-type pseudoknot of human telomerase RNA.

    abstract::Telomerase is a ribonucleoprotein complex that replicates the 3' ends of linear chromosomes by successive additions of telomere repeat DNA. The telomerase holoenzyme contains two essential components for catalysis, a telomerase reverse transcriptase (TERT) and telomerase RNA (TER). The TER includes a template for telo...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2008.10.005

    authors: Kim NK,Zhang Q,Zhou J,Theimer CA,Peterson RD,Feigon J

    更新日期:2008-12-31 00:00:00

  • Crystal structure of Hsc20, a J-type Co-chaperone from Escherichia coli.

    abstract::Hsc20 is a 20 kDa J-protein that regulates the ATPase activity and peptide-binding specificity of Hsc66, an hsp70-class molecular chaperone. We report herein the crystal structure of Hsc20 from Escherichia coli determined to a resolution of 1.8 A using a combination of single isomorphous replacement (SIR) and multi-wa...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.2000.4252

    authors: Cupp-Vickery JR,Vickery LE

    更新日期:2000-12-15 00:00:00

  • Mapping the energy landscape of repeat proteins using NMR-detected hydrogen exchange.

    abstract::Repeat proteins contain tandem arrays of a simple structural motif. In contrast to globular proteins, repeat proteins are stabilized only by interactions between residues that are relatively close together in the sequence, with no "long-range" interactions. Our work focuses on the tetratricopeptide repeat (TPR), a 34 ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2008.02.046

    authors: Cortajarena AL,Mochrie SG,Regan L

    更新日期:2008-06-06 00:00:00

  • Accomodation of S-cis-tamoxifen-N(2)-guanine adduct within a bent and widened DNA minor groove.

    abstract::The non-steroidal anti-estrogen tamoxifen [TAM] has been in clinical use over the last two decades as a potent adjunct chemotherapeutic agent for treatment of breast cancer. It has also been given prophylactically to women with a strong family history of breast cancer. However, tamoxifen treatment has also been associ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.2000.4071

    authors: Shimotakahara S,Gorin A,Kolbanovskiy A,Kettani A,Hingerty BE,Amin S,Broyde S,Geacintov N,Patel DJ

    更新日期:2000-09-15 00:00:00

  • X-ray structure of a dihydropyrimidinase from Thermus sp. at 1.3 A resolution.

    abstract::Dihydropyrimidinases (hydantoinases) catalyse the reversible hydrolytic ring-opening of cyclic diamides such as dihydropyrimidines in the catabolism of pyrimidines. In biotechnology, these enzymes find application in the enantiospecific production of amino acids from racemic hydantoins. The crystal structure of a D-en...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/S0022-2836(02)00422-9

    authors: Abendroth J,Niefind K,Schomburg D

    更新日期:2002-06-28 00:00:00

  • Efficient Catalysis of Protein Folding by GroEL/ES of the Obligate Chaperonin Substrate MetF.

    abstract::The cylindrical chaperonin GroEL and its cofactor GroES mediate ATP-dependent protein folding in Escherichia coli by transiently encapsulating non-native substrate in a nano-cage formed by the GroEL ring cavity and the lid-shaped GroES. Mechanistic studies of GroEL/ES with heterologous protein substrates suggested tha...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2020.02.031

    authors: Singh AK,Balchin D,Imamoglu R,Hayer-Hartl M,Hartl FU

    更新日期:2020-03-27 00:00:00

  • Crystal structure of the agrin-responsive immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK.

    abstract::Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed exclusively in skeletal muscle, where it is required for formation of the neuromuscular junction. MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. Here, we report the crystal structure of the agrin-responsive first and seco...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2006.09.019

    authors: Stiegler AL,Burden SJ,Hubbard SR

    更新日期:2006-12-01 00:00:00

  • Guided evolution of enzymes with new substrate specificities.

    abstract::A gene library was constructed coding for all possible variants of two amino acids (101, 102) in a solvent-exposed surface return loop (alpha E-beta D) of Bacillus stearothermophilus L-lactate dehydrogenase (bsLDH). All but one of 38 enzyme variants examined were thermally stable and had native-like hydrodynamic prope...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1996.0626

    authors: el Hawrani AS,Sessions RB,Moreton KM,Holbrook JJ

    更新日期:1996-11-22 00:00:00

  • Crystal structure of the C-terminal domain of S.cerevisiae eIF5.

    abstract::eIF5, a GTPase-activating protein (GAP) specific for eIF2, plays a critical role in pre-initiation complex assembly and correct AUG selection during eukaryotic translation initiation. eIF5 is involved in the formation of the multifactor complex (MFC), an important intermediate of the 43S pre-initiation complex. The C-...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2006.03.037

    authors: Wei Z,Xue Y,Xu H,Gong W

    更新日期:2006-05-26 00:00:00

  • Position-specific inhibition of yeast mitochondrial transcription by a poly(T) sequence.

    abstract::The 3' flanking nucleotide(s) of the octanucleotide promoter sequence regulates transcriptional efficiency of some mitochondrial genes in Saccharomyces cerevisiae. To understand this regulation the in vitro transcriptional activity of various synthetic mitochondrial promoters carrying different 3' flanking sequences w...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1997.1483

    authors: Biswas TK,Getz GS

    更新日期:1998-01-30 00:00:00

  • Ordered multi-site phosphorylation of the splicing factor ASF/SF2 by SRPK1.

    abstract::The human alternative splicing factor ASF/SF2, an SR (serine-arginine-rich) protein involved in mRNA splicing control, is activated by the multisite phosphorylation of its C-terminal RS domain, a segment containing numerous arginine-serine dipeptide repeats. The protein kinase responsible for this modification, SR-spe...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2007.08.029

    authors: Ma CT,Velazquez-Dones A,Hagopian JC,Ghosh G,Fu XD,Adams JA

    更新日期:2008-02-08 00:00:00

  • Secondary and tertiary structure formation of the beta-barrel membrane protein OmpA is synchronized and depends on membrane thickness.

    abstract::The mechanism of membrane insertion and folding of a beta-barrel membrane protein has been studied using the outer membrane protein A (OmpA) as an example. OmpA forms an eight-stranded beta-barrel that functions as a structural protein and perhaps as an ion channel in the outer membrane of Escherichia coli. OmpA folds...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/s0022-2836(02)01071-9

    authors: Kleinschmidt JH,Tamm LK

    更新日期:2002-11-22 00:00:00

  • Contributions of residue pairing to beta-sheet formation: conservation and covariation of amino acid residue pairs on antiparallel beta-strands.

    abstract::In an effort to better understand beta-sheet assembly, we have investigated the evolutionary behavior of neighboring residues on adjacent antiparallel beta-strands. Residue pairs were classified according to solvent exposure as well as by whether their backbone NH and C==O groups are hydrogen bonded. The conservation ...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.2000.4364

    authors: Mandel-Gutfreund Y,Zaremba SM,Gregoret LM

    更新日期:2001-02-02 00:00:00

  • A TfR-Binding Cystine-Dense Peptide Promotes Blood-Brain Barrier Penetration of Bioactive Molecules.

    abstract::The impenetrability of the blood-brain barrier (BBB) to most conventional drugs impedes the treatment of central nervous system (CNS) disorders. Interventions for diseases like brain cancer, neurodegeneration, or age-associated inflammatory processes require varied approaches to CNS drug delivery. Cystine-dense peptid...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2020.04.002

    authors: Crook ZR,Girard E,Sevilla GP,Merrill M,Friend D,Rupert PB,Pakiam F,Nguyen E,Yin C,Ruff RO,Hopping G,Strand AD,Finton KAK,Coxon M,Mhyre AJ,Strong RK,Olson JM

    更新日期:2020-06-26 00:00:00

  • Pulse-chase analysis of the in vivo assembly of the bacteriophage T4 tail.

    abstract::The in vivo assembly pathway of the complex tail of bacteriophage T4 virus was determined using pulse-chase analysis as a non-invasive alternative to the in vitro experiments previously used to map assembly. Bacteriophage T4 mutants defective in head assembly were used to infect cultures of Escherichia coli in order t...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.2000.3551

    authors: Ferguson PL,Coombs DH

    更新日期:2000-03-17 00:00:00

  • Close packing of an oligomeric eye lens beta-crystallin induces loss of symmetry and ordering of sequence extensions.

    abstract::beta-Crystallins are oligomeric eye lens proteins that are related to monomeric gamma-crystallins. The main sequence difference between the two families is the presence of sequence extensions in the beta-crystallins. A major question concerns the role that these extensions play in mediating interactions at the high pr...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(94)90025-6

    authors: Nalini V,Bax B,Driessen H,Moss DS,Lindley PF,Slingsby C

    更新日期:1994-03-04 00:00:00

  • Isolation of human antibody repertoires with preservation of the natural heavy and light chain pairing.

    abstract::The humoral immune system in higher vertebrates is unique in its ability to generate highly diverse antibody responses against most pathogens as well as against certain malignancies. Several technologies have been developed to exploit this vast source of potentially therapeutic antibodies, including hybridoma technolo...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2006.02.040

    authors: Meijer PJ,Andersen PS,Haahr Hansen M,Steinaa L,Jensen A,Lantto J,Oleksiewicz MB,Tengbjerg K,Poulsen TR,Coljee VW,Bregenholt S,Haurum JS,Nielsen LS

    更新日期:2006-05-05 00:00:00

  • High-resolution crystal structures of trimeric and rod phycocyanin.

    abstract::The phycobilisome light-harvesting antenna in cyanobacteria and red algae is assembled from two substructures: a central core composed of allophycocyanin surrounded by rods that always contain phycocyanin (PC). Unpigmented proteins called linkers are also found within the rods and core. We present here two new structu...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2010.10.036

    authors: David L,Marx A,Adir N

    更新日期:2011-01-07 00:00:00

  • Predicting Protein-Protein Interfaces that Bind Intrinsically Disordered Protein Regions.

    abstract::A long-standing goal in biology is the complete annotation of function and structure on all protein-protein interactions, a large fraction of which is mediated by intrinsically disordered protein regions (IDRs). However, knowledge derived from experimental structures of such protein complexes is disproportionately sma...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/j.jmb.2019.06.010

    authors: Wong ETC,Gsponer J

    更新日期:2019-08-09 00:00:00

  • Secondary structure model for the last two domains of single-stranded RNA phage Q beta.

    abstract::We have determined the nucleotide sequence of three positive single-stranded RNA coliphages and have used this information, together with the known sequences of the related phages Q beta and SP, to construct a secondary structure model for the two distal domains of Q beta RNA. The 3' terminal domain, which is about 10...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1006/jmbi.1995.0189

    authors: Beekwilder MJ,Nieuwenhuizen R,van Duin J

    更新日期:1995-04-14 00:00:00

  • Fibrinogen structure in projection at 18 A resolution. Electron density by co-ordinated cryo-electron microscopy and X-ray crystallography.

    abstract::Electron microscope images of frozen-hydrated crystals of a proteolytically modified fibrinogen show excellent preservation of the structure. An electron density map of the key centric projection of the crystal at 18 A resolution has been obtained by combining the phases derived from cryo-electron microscopy with X-ra...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(91)90739-s

    authors: Rao SP,Poojary MD,Elliott BW Jr,Melanson LA,Oriel B,Cohen C

    更新日期:1991-11-05 00:00:00

  • Intact ribonucleic acid from defective particles of bacteriophage R17.

    abstract::The growth of one group of amber mutants of R17 (class A) in non-permissive hosts results in a burst of bacteriophage-like particles, which are defective in that they are non-infectious. Here studies of particles produced by the growth of wild-type R17 and four class A mutants on AB301, a non-permissive Hfr Escherichi...

    journal_title:Journal of molecular biology

    pub_type: 杂志文章

    doi:10.1016/0022-2836(66)90016-7

    authors: Argetsinger JE,Gussin GN

    更新日期:1966-11-28 00:00:00