Cross-subunit interactions that stabilize open states mediate gating in NMDA receptors.

Abstract:

:NMDA receptors are excitatory channels with critical functions in the physiology of central synapses. Their activation reaction proceeds as a series of kinetically distinguishable, reversible steps, whose structural bases are currently under investigation. Very likely, the earliest steps include glutamate binding to glycine-bound receptors and subsequent constriction of the ligand-binding domain. Later, three short linkers transduce this movement to open the gate by mechanical pulling on transmembrane helices. Here, we used molecular and kinetic simulations and double-mutant cycle analyses to show that a direct chemical interaction between GluN1-I642 (on M3 helix) and GluN2A-L550 (on L1-M1 linker) stabilizes receptors after they have opened and thus represents one of the structural changes that occur late in the activation reaction. This native interaction extends the current decay, and its absence causes deficits in charge transfer by GluN1-I642L, a pathogenic human variant.

authors

Iacobucci GJ,Wen H,Helou M,Liu B,Zheng W,Popescu GK

doi

10.1073/pnas.2007511118

subject

Has Abstract

pub_date

2021-01-12 00:00:00

issue

2

eissn

0027-8424

issn

1091-6490

pii

2007511118

journal_volume

118

pub_type

杂志文章
  • Electroosmotic enhancement of the binding of a neutral molecule to a transmembrane pore.

    abstract::The flux of solvent water coupled to the transit of ions through protein pores is considerable. The effect of this electroosmotic solvent flow on the binding of a neutral molecule [beta-cyclodextrin (betaCD)] to sites within the staphylococcal alpha-hemolysin pore was investigated. Mutant alpha-hemolysin pores were us...

    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.2531778100

    authors: Gu LQ,Cheley S,Bayley H

    更新日期:2003-12-23 00:00:00

  • Ultraslow growth rates of giant gypsum crystals.

    abstract::Mineralogical processes taking place close to equilibrium, or with very slow kinetics, are difficult to quantify precisely. The determination of ultraslow dissolution/precipitation rates would reveal characteristic timing associated with these processes that are important at geological scale. We have designed an advan...

    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.1105233108

    authors: Van Driessche AE,García-Ruíz JM,Tsukamoto K,Patiño-Lopez LD,Satoh H

    更新日期:2011-09-20 00:00:00

  • Maternal transmission, sex ratio distortion, and mitochondria.

    abstract::In virtually all multicellular eukaryotes, mitochondria are transmitted exclusively through one parent, usually the mother. In this short review, we discuss some of the major consequences of uniparental transmission of mitochondria, including deleterious effects in males and selection for increased transmission throug...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.1421391112

    authors: Perlman SJ,Hodson CN,Hamilton PT,Opit GP,Gowen BE

    更新日期:2015-08-18 00:00:00

  • Myelination of peripheral nerves is controlled by PI4KB through regulation of Schwann cell Golgi function.

    abstract::Better understanding myelination of peripheral nerves would benefit patients affected by peripheral neuropathies, including Charcot-Marie-Tooth disease. Little is known about the role the Golgi compartment plays in Schwann cell (SC) functions. Here, we studied the role of Golgi in myelination of peripheral nerves in m...

    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.2007432117

    authors: Baba T,Alvarez-Prats A,Kim YJ,Abebe D,Wilson S,Aldworth Z,Stopfer MA,Heuser J,Balla T

    更新日期:2020-11-10 00:00:00

  • Regulation of T cell activation and tolerance by PDL2.

    abstract::T cell activation and tolerance are regulated by costimulatory molecules. Although PD-1 serves as a crucial negative regulator of T cells, the function of its ligands, PDL1 and PDL2, is still controversial. In this study, we created a PDL2-deficient mouse to characterize its function in T cell activation and tolerance...

    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.0601347103

    authors: Zhang Y,Chung Y,Bishop C,Daugherty B,Chute H,Holst P,Kurahara C,Lott F,Sun N,Welcher AA,Dong C

    更新日期:2006-08-01 00:00:00

  • The Hawthorne effect and energy awareness.

    abstract::The feeling of being observed or merely participating in an experiment can affect individuals' behavior. Referred to as the Hawthorne effect, this inconsistently observed phenomenon can both provide insight into individuals' behavior and confound the interpretation of experimental manipulations. Here, we pursue both 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.1301687110

    authors: Schwartz D,Fischhoff B,Krishnamurti T,Sowell F

    更新日期:2013-09-17 00:00:00

  • Diagnostic power of diffuse reflectance spectroscopy for targeted detection of breast lesions with microcalcifications.

    abstract::Microcalcifications geographically target the location of abnormalities within the breast and are of critical importance in breast cancer diagnosis. However, despite stereotactic guidance, core needle biopsy fails to retrieve microcalcifications in up to 15% of patients. Here, we introduce an approach based on diffuse...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 临床试验,杂志文章

    doi:10.1073/pnas.1215473110

    authors: Soares JS,Barman I,Dingari NC,Volynskaya Z,Liu W,Klein N,Plecha D,Dasari RR,Fitzmaurice M

    更新日期:2013-01-08 00:00:00

  • Proteomics approach to study the functions of Drosophila myosin VI through identification of multiple cargo-binding proteins.

    abstract::Myosin VI is a molecular motor implicated in many processes, and it likely associates with a variety of cargoes that specify its functions. Although it is critical to Drosophila development, little is known about its cellular roles. To reveal its involvement in specific pathways, we sought to identify the binding part...

    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.1101415108

    authors: Finan D,Hartman MA,Spudich JA

    更新日期:2011-04-05 00:00:00

  • Notch1 signaling plays a role in regulating precursor differentiation during CNS remyelination.

    abstract::In the developing CNS, Notch1 and its ligand, Jagged1, regulate oligodendrocyte differentiation and myelin formation, but their role in repair of demyelinating lesions in diseases such as multiple sclerosis remains unresolved. To address this question, we generated a mouse model in which we targeted Notch1 inactivatio...

    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.0902834106

    authors: Zhang Y,Argaw AT,Gurfein BT,Zameer A,Snyder BJ,Ge C,Lu QR,Rowitch DH,Raine CS,Brosnan CF,John GR

    更新日期:2009-11-10 00:00:00

  • DNA damage in stem cells activates p21, inhibits p53, and induces symmetric self-renewing divisions.

    abstract::DNA damage leads to a halt in proliferation owing to apoptosis or senescence, which prevents transmission of DNA alterations. This cellular response depends on the tumor suppressor p53 and functions as a powerful barrier to tumor development. Adult stem cells are resistant to DNA damage-induced apoptosis or senescence...

    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.1213394110

    authors: Insinga A,Cicalese A,Faretta M,Gallo B,Albano L,Ronzoni S,Furia L,Viale A,Pelicci PG

    更新日期:2013-03-05 00:00:00

  • Cyclin E, a redundant cyclin in breast cancer.

    abstract::Cyclin E is an important regulator of cell cycle progression that together with cyclin-dependent kinase (cdk) 2 is crucial for the G1/S transition during the mammalian cell cycle. Previously, we showed that severe overexpression of cyclin E protein in tumor cells and tissues results in the appearance of lower molecula...

    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.93.26.15215

    authors: Gray-Bablin J,Zalvide J,Fox MP,Knickerbocker CJ,DeCaprio JA,Keyomarsi K

    更新日期:1996-12-24 00:00:00

  • Dissociation and reassociation of immobilized porphobilinogen synthase: use of immobilized subunits for enzyme isolation.

    abstract::The dissociation and association of an immobilized preparation of the octameric enzyme porphobilinogen synthase [5-aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing), EC 4.2.1.24] is described. On treatment of the immobilized preparation with 4 M urea, four subunits per octamer are removed which can ...

    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.74.4.1383

    authors: Gurne D,Chen J,Shemin D

    更新日期:1977-04-01 00:00:00

  • Shear stress regulates the endothelial Kir2.1 ion channel.

    abstract::Endothelial cells (ECs) line the mammalian vascular system and respond to the hemodynamic stimulus of fluid shear stress, the frictional force produced by blood flow. When ECs are exposed to shear stress, one of the fastest responses is an increase of K(+) conductance, which suggests that ion channels are involved in ...

    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.102184999

    authors: Hoger JH,Ilyin VI,Forsyth S,Hoger A

    更新日期:2002-05-28 00:00:00

  • Region effects influence local tree species diversity.

    abstract::Global patterns of biodiversity reflect both regional and local processes, but the relative importance of local ecological limits to species coexistence, as influenced by the physical environment, in contrast to regional processes including species production, dispersal, and extinction, is poorly understood. Failure 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.1523683113

    authors: Ricklefs RE,He F

    更新日期:2016-01-19 00:00:00

  • The 3D NOESY-[(1)H,(15)N,(1)H]-ZQ-TROSY NMR experiment with diagonal peak suppression.

    abstract::In our 3D NOESY-[(1)H,(15)N,(1)H]-ZQ-TROSY experiment, the TROSY principle (transverse relaxation-optimized spectroscopy) is used in three-dimensional (3D) (15)N-resolved nuclear Overhauser enhancement spectroscopy (NOESY), which enables resonance assignments by sequential nuclear Overhauser effects and the collection...

    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.96.17.9607

    authors: Pervushin KV,Wider G,Riek R,Wüthrich K

    更新日期:1999-08-17 00:00:00

  • Human immunodeficiency virus (HIV) antigens: structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins.

    abstract::Molecular modeling and two-dimensional NMR techniques enable us to identify structural features in the third variable region (V3) loop of the human immunodeficiency virus (HIV) surface glycoprotein gp120, in particular the principal neutralizing determinant (PND), that remain conserved despite the sequence variation. ...

    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.92.1.315

    authors: Fontenot JD,Gatewood JM,Mariappan SV,Pau CP,Parekh BS,George JR,Gupta G

    更新日期:1995-01-03 00:00:00

  • Absence of unsaturated fatty acid synthesis in murine T lymphocytes.

    abstract::Stearic acid is toxic for T lymphocytes in vitro but has little effect on B lymphocytes. To investigate the molecular basis for this difference, purified murine T and B lymphocytes were compared for their abilities to incorporate and metabolize stearic acid. Unstimulated T and B cells incorporated identical amounts of...

    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.86.16.6133

    authors: Buttke TM,Van Cleave S,Steelman L,McCubrey JA

    更新日期:1989-08-01 00:00:00

  • Discovery and characterization of an epithelial-specific galectin in the endometrium that forms crystals in the trophectoderm.

    abstract::Secretions of the uterus support survival and growth of the conceptus (embryo/fetus and associated membranes) during pregnancy. Galectin-15, also known as OVGAL11 and a previously uncharacterized member of the galectin family of secreted beta-galactoside lectins containing a conserved carbohydrate recognition domain a...

    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.0402669101

    authors: Gray CA,Adelson DL,Bazer FW,Burghardt RC,Meeusen EN,Spencer TE

    更新日期:2004-05-25 00:00:00

  • Modification of severe coxsackievirus B 3 infection in marasmic mice by transfer of immune lymphoid cells.

    abstract::Coxsackievirus causes severe disease in adult mice subjected to sustained post-weaning undernutrition (marasmus). Virus-infected marasmic mice have an increased incidence of mortality, severe lesions, and elevated and persistent viral in target organs. Transfer of immune lymphoid cells 30 min or 24 hr after viral chal...

    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.68.9.2108

    authors: Woodruff JF,Woodruff JJ

    更新日期:1971-09-01 00:00:00

  • Addition of a photocrosslinking amino acid to the genetic code of Escherichiacoli.

    abstract::Benzophenones are among the most useful photocrosslinking agents in biology. We have evolved an orthogonal aminoacyl-tRNA synthetase/tRNA pair that makes possible the in vivo incorporation of p-benzoyl-l-phenylalanine into proteins in Escherichia coli in response to the amber codon, TAG. This unnatural amino acid was ...

    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.172226299

    authors: Chin JW,Martin AB,King DS,Wang L,Schultz PG

    更新日期:2002-08-20 00:00:00

  • Biogenesis of the pore architecture of a voltage-gated potassium channel.

    abstract::The pore domain of voltage-gated potassium (Kv) channels consists of transmembrane helices S5 and S6, the turret, the pore helix, the selectivity filter, and the loop preceding S6, with a tertiary reentrant structure between S5 and S6. Using biogenic intermediates, mass tagging (pegylation), and a molecular tape 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.1017097108

    authors: Gajewski C,Dagcan A,Roux B,Deutsch C

    更新日期:2011-02-22 00:00:00

  • Severed corticospinal axons recover electrophysiologic control of muscle activity after x-ray therapy in lesioned adult spinal cord.

    abstract::Mechanical injury to the adult mammalian spinal cord results in permanent loss of structural integrity at the lesion site and of the brain-controlled function distal to the lesion. Some of these consequences were permanently averted by altering the cellular constituents at the lesion site with x-irradiation delivered ...

    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.93.20.11185

    authors: Kalderon N,Fuks Z

    更新日期:1996-10-01 00:00:00

  • Newly identified and diverse plastid-bearing branch on the eukaryotic tree of life.

    abstract::The use of molecular methods is altering our understanding of the microbial biosphere and the complexity of the tree of life. Here, we report a newly discovered uncultured plastid-bearing eukaryotic lineage named the rappemonads. Phylogenies using near-complete plastid ribosomal DNA (rDNA) operons demonstrate that thi...

    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.1013337108

    authors: Kim E,Harrison JW,Sudek S,Jones MD,Wilcox HM,Richards TA,Worden AZ,Archibald JM

    更新日期:2011-01-25 00:00:00

  • Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA plus protein vaccination.

    abstract::It is generally thought that an effective vaccine to prevent HIV-1 infection should elicit both strong neutralizing antibody and cytotoxic T lymphocyte responses. We recently demonstrated that potent, boostable, long-lived HIV-1 envelope (Env)-specific cytotoxic T lymphocyte responses can be elicited in rhesus monkeys...

    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.94.17.9378

    authors: Letvin NL,Montefiori DC,Yasutomi Y,Perry HC,Davies ME,Lekutis C,Alroy M,Freed DC,Lord CI,Handt LK,Liu MA,Shiver JW

    更新日期:1997-08-19 00:00:00

  • Medial prefrontal cortex and striatum mediate the influence of social comparison on the decision process.

    abstract::We compared private and social decision making to investigate the neural underpinnings of the effect of social comparison on risky choices. We measured brain activity using functional MRI while participants chose between two lotteries: in the private condition, they observed the outcome of the unchosen lottery, and in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,随机对照试验

    doi:10.1073/pnas.1100892108

    authors: Bault N,Joffily M,Rustichini A,Coricelli G

    更新日期:2011-09-20 00:00:00

  • Macrophage migration inhibitory factor (MIF) exerts antifibrotic effects in experimental liver fibrosis via CD74.

    abstract::Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine that has been implicated in various inflammatory diseases. Chronic inflammation is a mainstay of liver fibrosis, a leading cause of morbidity worldwide, but the role of MIF in liver scarring has not yet been elucidated. Here we have un...

    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.1107023108

    authors: Heinrichs D,Knauel M,Offermanns C,Berres ML,Nellen A,Leng L,Schmitz P,Bucala R,Trautwein C,Weber C,Bernhagen J,Wasmuth HE

    更新日期:2011-10-18 00:00:00

  • Isoleucine 309 acts as a C4 catalytic switch that increases ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) carboxylation rate in Flaveria.

    abstract::Improving global yields of important agricultural crops is a complex challenge. Enhancing yield and resource use by engineering improvements to photosynthetic carbon assimilation is one potential solution. During the last 40 million years C(4) photosynthesis has evolved multiple times, enabling plants to evade the cat...

    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.1109503108

    authors: Whitney SM,Sharwood RE,Orr D,White SJ,Alonso H,Galmés J

    更新日期:2011-08-30 00:00:00

  • Coordinate occupancy of AP-1 sites in the vitamin D-responsive and CCAAT box elements by Fos-Jun in the osteocalcin gene: model for phenotype suppression of transcription.

    abstract::Osteocalcin, a bone-specific protein and marker of the mature osteoblast, is expressed only in nonproliferating osteoblasts in a mineralizing extracellular matrix, while type I collagen is expressed in proliferating cells. The nuclear proteins encoded by the c-fos and c-jun protooncogenes are expressed during the prol...

    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.87.24.9990

    authors: Owen TA,Bortell R,Yocum SA,Smock SL,Zhang M,Abate C,Shalhoub V,Aronin N,Wright KL,van Wijnen AJ

    更新日期:1990-12-01 00:00:00

  • Vaccinology in the post-COVID-19 era.

    abstract::The COVID-19 pandemic is a shocking reminder of how our world would look in the absence of vaccination. Fortunately, new technologies, the pace of understanding new and existing pathogens, and the increased knowledge of the immune system allow us today to develop vaccines at an unprecedented speed. Some of the vaccine...

    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.2020368118

    authors: Rappuoli R,De Gregorio E,Del Giudice G,Phogat S,Pecetta S,Pizza M,Hanon E

    更新日期:2021-01-19 00:00:00

  • Unique double-stranded fragments of bacteriophage T5 DNA resulting from preferential shear-induced breakage at nicks.

    abstract::Nicks within one strand of the bacteriophage T5 DNA molecule act as " weak points" for a novel kind mechanical breakage that can be utilized for "dissecting" the genome. The products from sheared T5(+) DNA include five unique double-stranded segments of the molecule and various combinations of adjacent segments. These...

    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.71.5.2108

    authors: Hayward GS

    更新日期:1974-05-01 00:00:00