Abstract:
:The 20S proteasome core particle (20S CP) plays an integral role in cellular homeostasis by degrading proteins no longer required for function. The process is, in part, controlled via gating residues localized to the ends of the heptameric barrel-like CP structure that occlude substrate entry pores, preventing unregulated degradation of substrates that might otherwise enter the proteasome. Previously, we showed that the N-terminal residues of the α-subunits of the CP from the archaeon Thermoplasma acidophilum are arranged such that, on average, two of the seven termini are localized inside the lumen of the proteasome, thereby plugging the entry pore and functioning as a gate. However, the mechanism of gating remains unclear. Using solution NMR and a labeling procedure in which a series of mixed proteasome rings are prepared such that the percentage of gate-containing subunits is varied, we address the energetics of gating and establish whether gating is a cooperative process involving the concerted action of residues from more than a single protomer. Our results establish that the intrinsic probability of a gate entering the lumen favors the in state by close to 20-fold, that entry of each gate is noncooperative, with the number of gates that can be accommodated inside the lumen a function of the substrate entry pore size and the bulkiness of the gating residues. Insight into the origin of the high affinity for the in state is obtained from spin-relaxation experiments. More generally, our approach provides an avenue for dissecting interactions of individual protomers in homo-oligomeric complexes.
journal_name
Proc Natl Acad Sci U S Aauthors
Huang R,Pérez F,Kay LEdoi
10.1073/pnas.1712297114subject
Has Abstractpub_date
2017-11-14 00:00:00pages
E9846-E9854issue
46eissn
0027-8424issn
1091-6490pii
1712297114journal_volume
114pub_type
杂志文章abstract::Mechanotransduction in the mammalian auditory system depends on mechanosensitive channels in the hair bundles that project from the apical surface of the sensory hair cells. Individual stereocilia within each bundle contain a core of tightly packed actin filaments, whose length is dynamically regulated during developm...
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.1304644110
更新日期:2013-08-20 00:00:00
abstract::The quantum mechanical problem of the hydrogen atom is treated by use of a finite difference equation in place of Schrödinger's differential equation. The exact solution leads to a wave vector energy expression that is readily converted to the Bohr-Rydberg formula. (The calculations here reported are limited to spheri...
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.83.16.5753
更新日期:1986-08-01 00:00:00
abstract::Sensory information from the external world is inherently ambiguous, necessitating prior experience as a constraint on perception. Prolonged experience (adaptation) induces perception of ambiguous morph faces as a category different from the adapted category, suggesting sensitivity in underlying neural codes to differ...
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.0702548104
更新日期:2007-08-14 00:00:00
abstract::Developmentally regulated genes in Drosophila, which are conserved through evolution, are potential candidates for key functions in biological processes such as cell cycle, programmed cell death, and cancer. We report cloning and characterization of the human homologue of the Drosophila seven in absentia gene (HUMSIAH...
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.93.17.9039
更新日期:1996-08-20 00:00:00
abstract::Childhood exposure to low-level lead can permanently reduce intelligence, but the neurobiologic mechanism for this effect is unknown. We examined the impact of lead exposure on the development of cortical columns, using the rodent barrel field as a model. In all areas of mammalian neocortex, cortical columns constitut...
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.97.10.5540
更新日期:2000-05-09 00:00:00
abstract::The content of elongation factor Tu in E. coli B has been determined both by radioimmune assay and by GDP binding. The two assays gave comparable results: cells growing at 2 doublings per hour contained about 8 molecules of Tu per ribosome, whereas those growing at 0.22 doublings per hour contained about 14 molecules ...
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.72.12.4780
更新日期:1975-12-01 00:00:00
abstract::The mechanism of preferential transmission (i.e., maternal inheritance) of cytoplasmic genes was investigated with chloroplast DNA of Chlamydomonas as a model system. The behavior of nuclear and chloroplast DNAs were compared in the sexual cycle; DNAs from male and female parents were distinguished by labeling with (1...
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.69.9.2410
更新日期:1972-09-01 00:00:00
abstract::The effect of RNA secondary structure on rho-independent and rho-dependent termination of transcription of T3 DNA by Escherichia coli RNA polymerase has been studied by incorporating, into nascent transcripts, base analogs that lead to altered base-pairing properties. A guanine --> hypoxanthine substitution, with atte...
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.76.4.1613
更新日期:1979-04-01 00:00:00
abstract::Insects living in the temperate zone enter a physiological state of arrested or slowed development to overcome an adverse season, such as winter. Developmental arrest, called diapause, occurs at a species-specific developmental stage, and embryonic and pupal diapauses have been extensively studied in mostly holometabo...
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.1922747117
更新日期:2020-03-10 00:00:00
abstract::Tephritid fruit flies belonging to the Rhagoletis pomonella sibling species complex are controversial because they have been proposed to diverge in sympatry (in the absence of geographic isolation) by shifting and adapting to new host plants. Here, we report evidence suggesting a surprising source of genetic 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.1730757100
更新日期:2003-09-02 00:00:00
abstract::The Mauer mandible, holotype of Homo heidelbergensis, was found in 1907 in fluvial sands deposited by the Neckar River 10 km southeast of Heidelberg, Germany. The fossil is an important key to understanding early human occupation of Europe north of the Alps. Given the associated mammal fauna and the geological context...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.1012722107
更新日期:2010-11-16 00:00:00
abstract::Conflicts of interest between the community and its members are at the core of human social dilemmas. If observed selfishness has future costs, individuals may hide selfish acts but display altruistic ones, and peers aim at identifying the most selfish persons to avoid them as future social partners. An interaction 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.1108996108
更新日期:2011-11-08 00:00:00
abstract::Night-shift workers are at high risk of drowsiness-related motor vehicle crashes as a result of circadian disruption and sleep restriction. However, the impact of actual night-shift work on measures of drowsiness and driving performance while operating a real motor vehicle remains unknown. Sixteen night-shift workers ...
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.1510383112
更新日期:2016-01-05 00:00:00
abstract::Homology-directed repair (HDR) is a critical pathway for the repair of DNA double-strand breaks (DSBs) in mammalian cells. Efficient HDR is thought to be crucial for maintenance of genomic integrity during organismal development and tumor suppression. However, most mammalian HDR studies have focused on transformed and...
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.1216824110
更新日期:2013-04-02 00:00:00
abstract::One of the issues currently being debated in the ongoing discussion of the pros and cons of today's globalization concerns the effects of greater world trade as well as of the changes in technology on a country's internal distribution of income, especially on skilled versus unskilled wage rates. In this article, I att...
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.1733335100
更新日期:2003-09-16 00:00:00
abstract::The adenovirus (Ad) early region 3 (E3) genes code for at least four proteins that inhibit the host immune responses mediated by cytotoxic T lymphocytes and tumor necrosis factor alpha. To evaluate the potential use of these immunoregulatory viral functions in facilitating allogeneic cell transplantation, the Ad E3 ge...
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.92.15.6947
更新日期:1995-07-18 00:00:00
abstract::Although adaptor ADAP (FYB) and its binding to SLP-76 has been implicated in TcR-induced "inside-out" signaling for LFA-1 activation in T cells, little is known regarding its role in LFA-1-mediated "outside-in" signaling. In this study, we demonstrate that ADAP and SLP-76-ADAP binding are coupled to LFA-1 costimulatio...
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.0900510106
更新日期:2009-07-28 00:00:00
abstract::By selective attachment of a DNA cleavage agent to specific residues in the yeast TATA box binding protein (yTBP), we demonstrate that, in solution, yTBP binds to the TATA boxes of both the adenovirus major late promoter and the yeast CYC1 promoter with only a modest preference in orientation and binds well to several...
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.94.25.13475
更新日期:1997-12-09 00:00:00
abstract::Phospholipase C-gamma1 (PLC-gamma1) contains two tandem Src homology 2 (SH2) domains. The NH(2)-terminal SH2 domain has been known to mediate the binding of PLC-gamma1 to receptor protein tyrosine kinases, which then activate PLC-gamma1 via phosphorylation at Y783. We now show that the phosphorylated Y783 residue (pY7...
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.0409590102
更新日期:2005-03-22 00:00:00
abstract::A selenium-containing protein, selenoprotein A, is an essential component of the clostridial glycine reductase complex. This enzyme complex catalyzes the reductive deamination of glycine, which is coupled to the esterification of orthophosphate resulting in the formation of ATP. Sequence information was obtained by au...
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.85.2.368
更新日期:1988-01-01 00:00:00
abstract::Blue mold of tobacco is caused by the fungus Peronospora tabacina. Its spores are released in the morning when the relative humidity falls, but they require free water for germination. Traditionally, the walls of the shade tents are raised to control the pathogen by drying leaves. We show that raising the walls does n...
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.79.2.697
更新日期:1982-01-01 00:00:00
abstract::In a previous study we demonstrated that vesicular stomatitis virus (VSV) can be used as a vector to express a soluble protein in mammalian cells. Here we have generated VSV recombinants that express four different membrane proteins: the cellular CD4 protein, a CD4-G hybrid protein containing the ectodomain of CD4 and...
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.93.21.11359
更新日期:1996-10-15 00:00:00
abstract::A specific lipoprotein of the E. coli outer membrane has been synthesized in a cell-free system directed by purified messenger RNA. The mRNA for the lipoprotein was purified as 7S RNA about 250-fold from exponentially growing cells. Protein synthesis of the cell-free system was totally dependent upon the addition of 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.71.10.4149
更新日期:1974-10-01 00:00:00
abstract::We present a phylogenetic analysis to determine whether a given tRNA molecule was established in evolution before its cognate aminoacyl-tRNA synthetase. The earlier appearance of tRNA versus their metabolically related enzymes is a prediction of the RNA world theory, but the available synthetase and tRNA sequences pre...
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.95.19.11295
更新日期:1998-09-15 00:00:00
abstract::Fibroblast growth factor 1 (FGF-1) is a potent angiogenic and neurotrophic factor whose structure lacks a classical signal sequence for secretion. Although the initiation of these biological activities involves the interaction between FGF-1 and cell surface receptors, the mechanism responsible for the regulation of FG...
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.89.22.10691
更新日期:1992-11-15 00:00:00
abstract::Two-dimensional 1H NMR investigations were used to locate elements of regular secondary structure in the human complement protein C3a (the des-Arg77 derivative) in solution. The results were compared to a refined crystal structure based on the 3.2-A resolution structure of des-Arg77-C3a [Huber, R., Scholze, H., Paques...
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.85.14.5036
更新日期:1988-07-01 00:00:00
abstract::1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes parkinsonism in humans and nonhuman animals, and its use has led to greater understanding of the pathogenesis of Parkinson's disease. However, its molecular targets have not been defined. We show that mice lacking the gene for poly(ADP-rib...
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.96.10.5774
更新日期:1999-05-11 00:00:00
abstract::Heparan sulfate regulates diverse cell-surface signaling events, and its roles in the development of the nervous system recently have been increasingly uncovered by studies using genetic models carrying mutations of genes encoding enzymes for its synthesis. On the other hand, the role of heparan sulfate in the physiol...
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.1117881109
更新日期:2012-03-27 00:00:00
abstract::Autoimmunity often involves the abnormal targeting of self-antigens by antibodies, leading to tissue destruction and other pathologies. This process could potentially be disrupted by small ligands that bind specifically to autoantibodies and inhibit their interaction with the target antigen. Here we report the identif...
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.92.6.2355
更新日期:1995-03-14 00:00:00
abstract::We provide a framework for structural multiscale geometric organization of graphs and subsets of R(n). We use diffusion semigroups to generate multiscale geometries in order to organize and represent complex structures. We show that appropriately selected eigenfunctions or scaling functions of Markov matrices, which d...
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.0500334102
更新日期:2005-05-24 00:00:00