Abstract:
:Antibodies provide effective antiviral immunity despite the fact that viruses escape into cells when they infect. Here we show that antibodies remain attached to viruses after cell infection and mediate an intracellular immune response that disables virions in the cytosol. We have discovered that cells possess a cytosolic IgG receptor, tripartite motif-containing 21 (TRIM21), which binds to antibodies with a higher affinity than any other IgG receptor in the human body. TRIM21 rapidly recruits to incoming antibody-bound virus and targets it to the proteasome via its E3 ubiquitin ligase activity. Proteasomal targeting leads to rapid degradation of virions in the cytosol before translation of virally encoded genes. Infection experiments demonstrate that at physiological antibody concentrations TRIM21 neutralizes viral infection. These results reveal an intracellular arm of adaptive immunity in which the protection mediated by antibodies does not end at the cell membrane but continues inside the cell to provide a last line of defense against infection.
journal_name
Proc Natl Acad Sci U S Aauthors
Mallery DL,McEwan WA,Bidgood SR,Towers GJ,Johnson CM,James LCdoi
10.1073/pnas.1014074107subject
Has Abstractpub_date
2010-11-16 00:00:00pages
19985-90issue
46eissn
0027-8424issn
1091-6490pii
1014074107journal_volume
107pub_type
杂志文章abstract::We have evaluated two synthetic epothilone analogues lacking the 12,13-epoxide functionality, 12,13-desoxyepothilone B (dEpoB), and 12,13-desoxyepothilone F (dEpoF). The concentrations required for 50% growth inhibition (IC(50)) for a variety of anticancer agents were measured in CCRF-CEM/VBL1000 cells (2,048-fold res...
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.131153098
更新日期:2001-07-03 00:00:00
abstract::Growing knowledge of the key molecular components involved in biological processes such as endocytosis, exocytosis, and motility has enabled direct testing of proposed mechanistic models by reconstitution. However, current techniques for building increasingly complex cellular structures and functions from purified com...
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.1016410108
更新日期:2011-06-07 00:00:00
abstract::Human breast cancers contain an RNA related to that of mouse mammary tumor virus. In 79% of the breast malignancies examined, this type of RNA is a 70S-component encapsulated with RNA-instructed DNA polymerase in a particle possessing the density characteristics of RNA tumor viruses. Further, the DNA synthesized by th...
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.69.11.3133
更新日期:1972-11-01 00:00:00
abstract::Extracts of insect cells infected with baculoviruses recombinant for the herpes simplex virus 1 (HSV-1)-encoded enzymes that are required for its replication can promote the rolling circle replication of circular plasmid templates. Replication is independent of a HSV-1 origin of replication (oris) or the HSV-1 origin ...
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.91.22.10665
更新日期:1994-10-25 00:00:00
abstract::Primary HIV-1 isolates were evaluated for their sensitivity to inhibition by beta-chemokines RANTES (regulated upon activation, normal T-cell expressed and secreted), macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta. Virus isolates of both nonsyncytium-inducing (NSI) and syncytium-inducing (SI) bi...
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.93.26.15382
更新日期:1996-12-24 00:00:00
abstract::XMAP215/Dis1 family proteins positively regulate microtubule growth. Repeats at their N termini, called TOG domains, are important for this function. While TOG domains directly bind tubulin dimers, it is unclear how this interaction translates to polymerase activity. Understanding the functional roles of TOG domains i...
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.1016498108
更新日期:2011-02-15 00:00:00
abstract::Ocean acidification represents a key threat to coral reefs by reducing the calcification rate of framework builders. In addition, acidification is likely to affect the relationship between corals and their symbiotic dinoflagellates and the productivity of this association. However, little is known about how acidificat...
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.0804478105
更新日期:2008-11-11 00:00:00
abstract::Double-stranded oligodeoxynucleotides that represent protein binding sites in the regulatory regions of the mouse genes encoding transthyretin (TTR) and alpha 1-antitrypsin (alpha 1-AT) bound a nuclear protein factor(s) found mainly in hepatocytes. A site in the regulatory region of the gene encoding rat serum albumin...
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.85.11.3840
更新日期:1988-06-01 00:00:00
abstract::Serotonin (5-HT) plays a key role in early brain development, and manipulation of 5-HT levels during this period can have lasting neurobiological and behavioral consequences. It is unclear how perinatal exposure to drugs, such as selective serotonin reuptake inhibitors (SSRIs), impacts cortical neural network function...
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.1109353108
更新日期:2011-11-08 00:00:00
abstract::Certain mutations at the glaB locus result in the failure to fully derepress glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] and to convert it to the active nonadenylylated form in response to nitrogen limitation. In these mutants the PII regulatory protein is altered such that it cannot be...
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.77.5.2636
更新日期:1980-05-01 00:00:00
abstract::Bloom syndrome is a disorder of profound and early cancer predisposition in which cells become hypermutable, exhibit high frequency of sister chromatid exchanges, and show increased micronuclei. BLM, the gene mutated in Bloom syndrome, has been cloned previously, and the BLM protein is a member of the RecQ family of 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.1431624100
更新日期:2003-07-08 00:00:00
abstract::The temperature dependence of migration rate and of the thermotactic sensitivity of pseudoplasmodia of Dictyostelium discoideum has been measured. Migration rate increases with temperature to 20 degrees, is temperature insensitive from 20 degrees to 27.5 degrees, and decreases with temperature to 29 degrees, above whi...
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.74.5.2007
更新日期:1977-05-01 00:00:00
abstract::Peptide ligand selection by MHC class I molecules, which occurs by iterative optimization, is the centerpiece of immunodominance in antiviral and antitumor immune responses. For its understanding, the molecular mechanisms of peptide binding and dissociation by class I molecules must be elucidated. To this end, we have...
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.1418690112
更新日期:2015-01-06 00:00:00
abstract::The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize 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.84.24.9214
更新日期:1987-12-01 00:00:00
abstract::Primary prostate cancer is the most common malignancy in men but has highly variable outcomes, highlighting the need for biomarkers to determine which patients can be managed conservatively. Few large prostate oncogenome resources currently exist that combine the molecular and clinical outcome data necessary to discov...
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.1411446111
更新日期:2014-07-29 00:00:00
abstract::The development of the luminescence system in Beneckea harveyi is controlled by cyclic nucleotides at the level of transcription. In the wild type, it is repressed by exogenously added guanosine 3':5'-cyclic monophosphate and this repression is overcome by the addition of adenosine 3':5'-cyclic monophosphate. These ob...
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.73.12.4454
更新日期:1976-12-01 00:00:00
abstract::The paucity of knowledge about cardiomyocyte maturation is a major bottleneck in cardiac regenerative medicine. In development, cardiomyocyte maturation is characterized by orchestrated structural, transcriptional, and functional specializations that occur mainly at the perinatal stage. Sarcomeres are the key cytoskel...
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.2008861118
更新日期:2021-01-12 00:00:00
abstract::In humans, spontaneous movements are often preceded by early brain signals. One such signal is the readiness potential (RP) that gradually arises within the last second preceding a movement. An important question is whether people are able to cancel movements after the elicitation of such RPs, and if so until which po...
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.1513569112
更新日期:2016-01-26 00:00:00
abstract::A tandemly repeated DNA sequence organized predominantly, if not entirely, in a specific manner on the human X chromosome has been cloned in pBR322 and characterized. The sequence was detected as a 2-kilobase band in ethidium bromide-stained agarose gels of BamHI-digested total human nuclear DNA. Although in situ hybr...
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.79.21.6593
更新日期:1982-11-01 00:00:00
abstract::We have asked here how the remarkable variation in maize haplotype structure affects recombination. We compared recombination across a genetic interval of 9S in 2 highly dissimilar heterozygotes that shared 1 parent. The genetic interval in the common haplotype is approximately 100 kb long and contains 6 genes intersp...
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.0902972106
更新日期:2009-05-26 00:00:00
abstract::The his4 region of yeast contains the information necessary for the catalysis of three steps in the histidine biosynthetic pathway. The three activities specified by this region remain physically associated during gel filtration and ultracentrifugation and after extensive purification. Nonsense mutations in the "opera...
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.63.4.1198
更新日期:1969-08-01 00:00:00
abstract::Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host-defense responses in certain bacterial infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to Pseudomonas ae...
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.1908816116
更新日期:2019-10-08 00:00:00
abstract::Hydrogen bonds and their relative strengths in proteins are of importance for understanding protein structure and protein motions. The correct strength of such hydrogen bonds is experimentally known to vary greatly from approximately 5-6 kcal/mol for the isolated bond to approximately 0.5-1.5 kcal/mol for proteins 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.2133366100
更新日期:2003-10-28 00:00:00
abstract::The free radicals nitric oxide and superoxide anion react to form peroxynitrite (ONOO-), a highly toxic oxidant species. In vivo formation of ONOO- has been demonstrated in shock and inflammation. Herein we provide evidence that cytotoxicity in cells exposed to ONOO- is mediated by DNA strand breakage and the subseque...
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.93.5.1753
更新日期:1996-03-05 00:00:00
abstract::The structure of the gene encoding human hexabrachion (tenascin) has been determined from overlapping clones isolated from a human genomic bacteriophage library. The genomic inserts were characterized by restriction mapping, Southern blot analysis, PCR, and DNA sequencing. The coding region of the hexabrachion gene 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.88.21.9438
更新日期:1991-11-01 00:00:00
abstract::To understand complex biological systems, such as the development of multicellular organisms, it is important to characterize the gene expression dynamics. However, there is currently no universal technique for targeted insertion of reporter genes and quantitative imaging in multicellular model systems. Recently, geno...
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.1202768109
更新日期:2012-07-03 00:00:00
abstract::Apurinic/apyrimidinic (AP) sites are common DNA lesions that arise from spontaneous depurination or by base excision repair (BER) of modified bases. A biotin-containing aldehyde-reactive probe (ARP) [Kubo, K., Ide, H., Wallace, S. S. & Kow, Y. W. (1992) Biochemistry 31, 3703-3708] is used to measure AP sites in living...
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.97.2.686
更新日期:2000-01-18 00:00:00
abstract::A line of nonobese diabetic (NOD) mice expressing the human diabetes-associated HLA-DQ8 transgene in the absence of mouse IAbeta failed to show spontaneous insulitis or diabetes, but rather developed dilated cardiomyopathy, leading to early death from heart failure. Pathology in these animals results from an organ- an...
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.2235552100
更新日期:2003-11-11 00:00:00
abstract::In skeletal muscle, dihydropyridine receptors are functionally coupled to ryanodine receptors of the sarcoplasmic reticulum in triadic or diadic junctional complexes. In cardiac muscle direct physical or functional couplings have not been demonstrated. We have tested the hypothesis of functional coupling of L-type Ca2...
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.92.1.121
更新日期:1995-01-03 00:00:00
abstract::In everyday listening, sound reaches our ears directly from a source as well as indirectly via reflections known as reverberation. Reverberation profoundly distorts the sound from a source, yet humans can both identify sound sources and distinguish environments from the resulting sound, via mechanisms that remain uncl...
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.1612524113
更新日期:2016-11-29 00:00:00