Abstract:
:Undesired side products of DNA transfections are usually discarded. However, here, we show that such products may provide insight into mutational events that are also a major driving force in protein evolution. While studying the small heat-shock protein alphaA-crystallin, we transfected the hamster alphaA-crystallin gene into a mouse muscle cell line. One of the stable transfected cell lines expressed, in addition to the expected normal alphaA- and alternatively spliced alphaAins-crystallins, two slightly larger, immunologically cross-reacting proteins. These proteins were found to be encoded by a mutant alphaA-crystallin gene with a large intragenic duplication, arisen by illegitimate recombination at two CCCAT homologies, approximately 1.8 kilobases apart in the normal hamster alphaA-crystallin gene. As a consequence, a tandem-duplicated exon 3 sequence is present in the mature mRNA of this gene, resulting in a 41-residue repeat in the translated proteins. Cells expressing the elongated alphaA-crystallins have normal growth characteristics and the usual diffuse cytoplasmic distribution of immunoreactive alphaA-crystallin. Size-exclusion chromatography of cell extracts indicated that the mutant proteins are readily incorporated into the normal large water-soluble alphaA-crystallin complexes, showing that the insert does not disturb the integrity of these complexes. This viable alphaA-crystallin mutant thus mimics the origins and effects of exon duplication, which is a common consequence of exon shuffling in mammalian genome evolution.
journal_name
Proc Natl Acad Sci U S Aauthors
van Rijk AA,de Jong WW,Bloemendal Hdoi
10.1073/pnas.96.14.8074keywords:
subject
Has Abstractpub_date
1999-07-06 00:00:00pages
8074-9issue
14eissn
0027-8424issn
1091-6490journal_volume
96pub_type
杂志文章abstract::A synchronized heart beat is controlled by pacemaking impulses conducted through Purkinje fibers. In chicks, these impulse-conducting cells are recruited during embryogenesis from myocytes in direct association with developing coronary arteries. In culture, the vascular cytokine endothelin converts embryonic myocytes ...
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.96.23.13214
更新日期:1999-11-09 00:00:00
abstract::Here, we describe the identification and characterization of a nuclear body (matrix-associated deacetylase body) whose formation and integrity depend on deacetylase activity. Typically, there are 20-40 0.5-microM bodies per nucleus, although the size and number can vary substantially. The structure appears to contain ...
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.97.19.10330
更新日期:2000-09-12 00:00:00
abstract::The six individual catalytic polypeptide chains within the two catalytic trimers of Escherichia coli aspartate transcarbamoylase (ATCase; EC 2.1.3.2) are folded into two discrete structural domains interconnected in part by helix 12, which comprises residues 285-305 and is located near the carboxyl terminus of the cha...
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.88.2.458
更新日期:1991-01-15 00:00:00
abstract::T cells are essential for immune defenses against pathogens, such that viability of naïve T cells before antigen encounter is critical to preserve a polyclonal repertoire and prevent immunodeficiencies. The viability of naïve T cells before antigen recognition is ensured by IL-7, which drives expression of the prosurv...
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.1315398111
更新日期:2014-05-20 00:00:00
abstract::Biologists regularly search databases of DNA or protein sequences for evolutionary or functional relationships to a given query sequence. We describe a ranking algorithm that exploits the entire network structure of similarity relationships among proteins in a sequence database by performing a diffusion operation on 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.0308067101
更新日期:2004-04-27 00:00:00
abstract::Human infections with Ebola virus (EBOV) result in a deadly viral disease known as Ebola hemorrhagic fever. Up to 90% of infected patients die, and there is no available treatment or vaccine. The sporadic human outbreaks are believed to result when EBOV "jumps" from an infected animal to a person and is subsequently 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.0809698105
更新日期:2008-11-18 00:00:00
abstract::The binding of small molecules to distinctive three-dimensional structures in mRNA provides a new dimension in RNA control, previously limited to the targeting of secondary structures with antisense and RNA interference; such targeting can modulate mRNA function and rates of protein biosynthesis. Small molecules that ...
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.0509744102
更新日期:2006-01-10 00:00:00
abstract::A weakly nonlinear oscillator of natural frequency omega(0) and damping ratio delta is driven by an amplitude-modulated force of dimensionless amplitude epsilon, carrier frequency omega, and modulation frequency omega(1). Each of (omega - omega(0))/omega(0), omega(1)/omega(0), and delta is O(epsilon(2/3)) as epsilon -...
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.81.12.3919
更新日期:1984-06-01 00:00:00
abstract::Nerve growth factor (NGF) serum levels were measured in 49 patients with asthma and/or rhinoconjunctivitis and/or urticaria-angioedema. Clinical and biochemical parameters, such as bronchial reactivity, total and specific serum IgE levels, and circulating eosinophil cationic protein levels, were evaluated in relation ...
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.93.20.10955
更新日期:1996-10-01 00:00:00
abstract::Modification by covalent attachment of polyethylene glycol (PEG) can reduce the immunogenicity and prolong the circulating life of proteins, but the utility of this approach for any protein is restricted by the number and distribution of PEG attachment sites (e.g., epsilon-amino groups of lysine residues). We have dev...
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.88.16.7185
更新日期:1991-08-15 00:00:00
abstract::The origin recognition complex (ORC) binds sites from which DNA replication is initiated. We address ORC binding selectivity in vivo by mapping ∼52,000 ORC2 binding sites throughout the human genome. The ORC binding profile is broader than those of sequence-specific transcription factors, suggesting that ORC is not bo...
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.1609060113
更新日期:2016-08-16 00:00:00
abstract::The fluorescence decay of the rare earth terbium when bound to the protein calmodulin changes from a simple exponential decay to a complex nonexponential decay as the temperature is lowered below 200 K. We have fit the observed decay curves by assuming that the terbium emission is a forced electric dipole transition 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.84.6.1541
更新日期:1987-03-01 00:00:00
abstract::A careful review of the literature in political science and neighboring social science disciplines shows that prevailing assumptions in the international development policy community about improved governance as a principal mechanism to reduce poverty in Africa rests more on faith than science. Conventional policy mod...
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.0700696104
更新日期:2007-10-23 00:00:00
abstract::The minimal size of the recombination site required for efficient FLP recombinase-catalyzed recombination in vitro is no more than 28 base pairs, which includes parts of two 13-base-pair inverted repeats and all of an 8-base-pair spacer. The FLP recombinase cleaves the DNA at the boundaries of the spacer, becomes cova...
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.82.21.7270
更新日期:1985-11-01 00:00:00
abstract::Photosystem I (PSI) reaction centers (RCs) of the thermophilic cyanobacterium Mastigocladus laminosus were purified and characterized. The PSI RC was obtained in two forms, monomeric and trimeric. The two forms contained the same number of pigments per P700 and displayed similar photochemical activities. The two forms...
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.88.12.5312
更新日期:1991-06-15 00:00:00
abstract::Human embryonic zeta-globin chains are alpha-globin-like chains that are normally present during the first three months of gestation. In this investigation, zeta-globin chains measured by a specific and sensitive radioimmunoassay and by an electrophoretic technique were found to be present in all 7 patients studied wi...
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.81.19.6188
更新日期:1984-10-01 00:00:00
abstract::We have investigated the role of Sonic hedgehog (Shh) in the development of facial structures by depriving chicken embryos of the most anterior sources of this morphogen, including the prechordal plate and the anterior ventral endoderm of the foregut, before the onset of neural crest cell (NCC) migration to the first ...
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.0604751103
更新日期:2006-08-01 00:00:00
abstract::Knowledge of the relative contributions of different water sources to intracellular fluids and body water is important for many fields of study, ranging from animal physiology to paleoclimate. The intracellular fluid environment of cells is challenging to study due to the difficulties of accessing and sampling the con...
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.1521038113
更新日期:2016-05-24 00:00:00
abstract::That tumors cause changes in surrounding tissues is well documented, but whether they also affect distant tissues is uncertain. Such knowledge may be important in understanding the relationship between cancer and overall patient health. To address this question, we examined tissues distant to sites of implanted tumors...
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.1008260107
更新日期:2010-10-19 00:00:00
abstract::Coatomer, the major component of the coat of COPI transport vesicles, binds both to the dilysine motif of resident membrane proteins of the endoplasmic reticulum and to the cytoplasmic domain of p23, a major type I membrane protein of COPI vesicles. Using a photocrosslinking approach, we find that under native conditi...
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.95.20.11649
更新日期:1998-09-29 00:00:00
abstract::Collagen fibrils can exceed thousands of microns in length and are therefore the longest, largest, and most size-pleomorphic protein polymers in vertebrates; thus, knowing how cells transport collagen fibrils is essential for a more complete understanding of protein transport and its role in tissue morphogenesis. Here...
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.1314348110
更新日期:2013-12-03 00:00:00
abstract::The role of copper/zinc-containing superoxide dismutase (cSOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) in metabolic defense against O2 toxicity in Drosophila is examined through the properties of a mutant strain carrying a cSOD-null mutation, cSODn108. Homozygotes are viable as larvae, which indicates that ...
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.86.8.2761
更新日期:1989-04-01 00:00:00
abstract::The segmented body plan of vertebrates is prefigured by reiterated embryonic mesodermal structures called somites. In the mouse embryo, timely somite formation from the presomitic mesoderm (PSM) is controlled by the "segmentation clock," a molecular oscillator that triggers progressive waves of Notch activity througho...
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.1222115110
更新日期:2013-05-28 00:00:00
abstract::The O(2)-reaction chemistry of 1:1 mixtures of (F(8))Fe(II) (1; F(8) = tetrakis(2,6-diflurorophenyl)porphyrinate) and [(L(Me(2))N)Cu(I)](+) (2; L(Me(2))N = N,N-bis(2-[2-(N',N'-4-dimethylamino)pyridyl]ethyl)methylamine) is described, to model aspects of the chemistry occurring in cytochrome c oxidase. Spectroscopic inv...
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.0737180100
更新日期:2003-04-01 00:00:00
abstract::Down syndrome (DS) caused by trisomy of chromosome 21 is the most common genetic cause of intellectual disability. Although the prenatal diagnosis of DS has become feasible, there are no therapies available for the rescue of DS-related neurocognitive impairment. A growth inducer newly identified in our screen of neura...
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.1704143114
更新日期:2017-09-19 00:00:00
abstract::Complement membrane attack complexes (MACs) promote inflammatory functions in endothelial cells (ECs) by stabilizing NF-κB-inducing kinase (NIK) and activating noncanonical NF-κB signaling. Here we report a novel endosome-based signaling complex induced by MACs to stabilize NIK. We found that, in contrast to cytokine-...
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.1503535112
更新日期:2015-08-04 00:00:00
abstract::While 9-O-acetylation of sialic acids has been reported in some mammalian tissues, the distribution of this modification on specific cell types and molecules is largely unknown. The influenza C virus hemagglutinin-esterase is a membrane-bound glycoprotein that binds specifically to 9-O-acetylated sialic acids (hemaggl...
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.91.16.7782
更新日期:1994-08-02 00:00:00
abstract::Bacterial transpeptidase and transglycosylase on the surface are essential for cell wall synthesis, and many antibiotics have been developed to target the transpeptidase; however, the problem of antibiotic resistance has arisen and caused a major threat in bacterial infection. The transglycosylase has been considered ...
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.1203900109
更新日期:2012-04-24 00:00:00
abstract::Despite a growing number of ion channel genes implicated in hereditary ataxia, it remains unclear how ion channel mutations lead to loss-of-function or death of cerebellar neurons. Mutations in the gene KCNMA1, encoding the α-subunit of the BK channel have emerged as responsible for a variety of neurological phenotype...
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.1920008117
更新日期:2020-03-17 00:00:00
abstract::Progressive myoclonus epilepsy of Univerricht-Lundborg type is a clinically defined entity among the progressive myoclonus epilepsies. It is an autosomal recessive disorder. The underlying biochemical defect is unknown. We used linkage analysis to localize the gene in 12 families with the aid of polymorphic DNA marker...
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.88.9.3696
更新日期:1991-05-01 00:00:00