Abstract:
:Small, single-module proteins that fold in a single cooperative step may be paradigms for understanding early events in protein-folding pathways generally. Recent experimental studies of the 64-residue chymotrypsin inhibitor 2 (CI2) support a nucleation mechanism for folding, as do some computer stimulations. CI2 has a nucleation site that develops only in the transition state for folding. The nucleus is composed of a set of adjacent residues (an alpha-helix), stabilized by long-range interactions that are formed as the rest of the protein collapses around it. A simple analysis of the optimization of the rate of protein folding predicts that rates are highest when the denatured state has little residual structure under physiological conditions and no intermediates accumulate. This implies that any potential nucleation site that is composed mainly of adjacent residues should be just weakly populated in the denatured state and become structured only in a high-energy intermediate or transition state when it is stabilized by interactions elsewhere in the protein. Hierarchical mechanisms of folding in which stable elements of structure accrete are unfavorable. The nucleation-condensation mechanism of CI2 fulfills the criteria for fast folding. On the other hand, stable intermediates do form in the folding of more complex proteins, and this may be an unavoidable consequence of increasing size and nucleation at more than one site.
journal_name
Proc Natl Acad Sci U S Aauthors
Fersht ARdoi
10.1073/pnas.92.24.10869subject
Has Abstractpub_date
1995-11-21 00:00:00pages
10869-73issue
24eissn
0027-8424issn
1091-6490journal_volume
92pub_type
杂志文章abstract::Inwardly rectifying potassium (K(+)) channels gated by G proteins (Kir3.x family) are widely distributed in neuronal, atrial, and endocrine tissues and play key roles in generating late inhibitory postsynaptic potentials, slowing the heart rate and modulating hormone release. They are directly activated by G(betagamma...
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.080572297
更新日期:2000-05-09 00:00:00
abstract::The supposition that agricultural intensification results in land sparing for conservation has become central to policy formulations across the tropics. However, underlying assumptions remain uncertain and have been little explored in the context of conservation incentive schemes such as policies for Reducing Emission...
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.1220070110
更新日期:2013-05-07 00:00:00
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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.1715336115
更新日期:2018-03-27 00:00:00
abstract::The protein CopC from Pseudomonas syringae has been found capable of binding copper(I) and copper(II) at two different sites, occupied either one at a time or simultaneously. The protein, consisting of 102 amino acids, is known to bind copper(II) in a position that is now found consistent with a coordination arrangeme...
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.0636904100
更新日期:2003-04-01 00:00:00
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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.91.9.3637
更新日期:1994-04-26 00:00:00
abstract::We have examined the effects of a stromal cell-derived cytokine designated interleukin 11 (IL-11) on the proliferation of murine hemopoietic progenitors in methylcellulose culture. COS cell-conditioned medium containing IL-11 supported formation of granulocyte/macrophage colonies and a small number of multilineage col...
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.88.3.765
更新日期:1991-02-01 00:00:00
abstract::The embryonic development of the optic nerve of the zebrafish, Brachydanio rerio, was studied by three-dimensional computer reconstruction from serial section electron micrographs. Growing fibers from retinal ganglion cells had growth cones in contact with more mature fibers from adjacent cell bodies. In the observed ...
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.77.7.4374
更新日期:1980-07-01 00:00:00
abstract::Duodenal bicarbonate secretion (DBS) is accepted as the primary mucosal defense against acid discharged from the stomach and is impaired in patients with duodenal ulcer disease. The secretory response to luminal acid is the main physiological stimulus for DBS and involves mediation by PGE2 produced by mucosal cells. 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.0508007102
更新日期:2005-10-18 00:00:00
abstract::A gene's expression pattern provides clues to its role in normal physiology and disease. To provide quantitative expression levels on a genome-wide scale, the Cancer Genome Anatomy Project (CGAP) uses serial analysis of gene expression (SAGE). Over 5 million transcript tags from more than 100 human cell types have bee...
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.152324199
更新日期:2002-08-20 00:00:00
abstract::Because xenon NMR is highly sensitive to the local environment, laser-polarized xenon could be a unique probe of living tissues. Realization of clinical and medical science applications beyond lung airspace imaging requires methods of efficient delivery of laser-polarized xenon to tissues, because of the short spin-la...
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.94.26.14725
更新日期:1997-12-23 00:00:00
abstract::Primates can store sensory stimulus parameters in working memory for subsequent manipulation, but until now, there has been no demonstration of this capacity in rodents. Here we report tactile working memory in rats. Each stimulus is a vibration, generated as a series of velocity values sampled from a normal distribut...
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.1315171111
更新日期:2014-02-11 00:00:00
abstract::The NOVH protein belongs to the emerging CCN [Connective tissue growth factor (CTGF), Cyr61/Cef10, nephroblastoma overexpressed gene] family of growth regulators sharing a strikingly conserved multimodular organization but exhibiting distinctive functional features. Two members of the family (CYR61 and CTGF) are posit...
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.96.3.869
更新日期:1999-02-02 00:00:00
abstract::A stable complex between pentaammineruthenium(III) and histidine-33 in horse heart ferricytochrome c is formed in the reaction between aquopentaammineruthenium(II) and the protein at pH 7. HPLC of the tryptic hydrolysate of the modified protein was employed to identify the pentaammineruthenium binding site. Spectrosco...
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.79.22.7052
更新日期:1982-11-01 00:00:00
abstract::Infection by certain human papillomavirus types is regarded as the major risk factor in the development of cervical cancer, one of the most common cancers of women worldwide. Analysis of the immunogenic and structural features of papillomavirus virions has been hampered by the inability to efficiently propagate the vi...
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.89.24.12180
更新日期:1992-12-15 00:00:00
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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.1214848109
更新日期:2012-11-20 00:00:00
abstract::In the absence of adaptive immunity displayed by animals, plants respond locally to biotic challenge via inducible basal defense networks activated through recognition and response to conserved pathogen-associated molecular patterns. In addition, immunity can be induced in tissues remote from infection sites by system...
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.0605423104
更新日期:2007-01-16 00:00:00
abstract::RNA molecules perform diverse regulatory functions in natural biological systems, and numerous synthetic RNA-based control devices that integrate sensing and gene-regulatory functions have been demonstrated, predominantly in bacteria and yeast. Despite potential advantages of RNA-based genetic control strategies in cl...
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.1001721107
更新日期:2010-05-11 00:00:00
abstract::Staphylococcus aureus surface protein SasG promotes cell-cell adhesion during the accumulation phase of biofilm formation, but the molecular basis of this interaction remains poorly understood. Here, we unravel the mechanical properties of SasG on the surface of living bacteria, that is, in its native cellular environ...
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.1519265113
更新日期:2016-01-12 00:00:00
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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.1114235109
更新日期:2012-03-27 00:00:00
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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.95.19.11241
更新日期:1998-09-15 00:00:00
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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.87.5.1899
更新日期:1990-03-01 00:00:00
abstract::We have isolated lentivirus strains that are related to the human immunodeficiency virus (HIV) from African green monkeys (Cercopithecus aethiops; AGM). Although immunologically related, these SIVagm are clearly distinct from other simian immunodeficiency virus (SIV) isolates, including isolates from Macaca mulatta (S...
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.86.8.2892
更新日期:1989-04-01 00:00:00
abstract::The Atg20 and Snx4/Atg24 proteins have been identified in a screen for mutants defective in a type of selective macroautophagy/autophagy. Both proteins are connected to the Atg1 kinase complex, which is involved in autophagy initiation, and bind phosphatidylinositol-3-phosphate. Atg20 and Snx4 contain putative BAR dom...
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.1708367114
更新日期:2017-11-21 00:00:00
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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.0405509101
更新日期:2004-11-23 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a ravaging condition of progressive lung scarring and destruction. Anti-inflammatory therapies including corticosteroids have limited efficacy in this ultimately fatal disorder. An important unmet need is to identify new agents that interact with key ...
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.1001520107
更新日期:2010-08-10 00:00:00
abstract::Metallothionein (MT) has several putative roles in metal detoxification, in Zn and Cu homeostasis, in scavenging free radicals, and in the acute phase response. Mice of mixed 129/Ola and C57BL/6J background with targeted disruption of MT-I and MT-II genes are more sensitive to toxic metals and oxidative stress. We not...
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.95.1.358
更新日期:1998-01-06 00:00:00
abstract::microRNAs comprise a few percent of animal genes and have been recognized as important regulators of a diverse range of biological processes. Understanding the biological functions of miRNAs requires effective means to identify their targets. Combined efforts from computational prediction, miRNA over-expression or dep...
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.0908149106
更新日期:2009-09-01 00:00:00
abstract::Chemokine homologs are encoded by many large DNA viruses, suggesting that they contribute to control of host leukocyte transmigration and trafficking during viral infection. Murine cytomegalovirus carries a CC (beta) chemokine homolog gene giving rise to two related proteins, murine cytomegalovirus chemokine 1 and 2 (...
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.96.19.10881
更新日期:1999-09-14 00:00:00
abstract::The tumor suppressor protein p53 plays a crucial role in coordinating cellular processes, such as cell cycle arrest, apoptosis, and senescence. The nerve injury-induced protein 1 (Ninjurin1, Ninj1) is a homophilic adhesion molecule and involved in nerve regeneration. Interestingly, Ninj1 is found to be overexpressed 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.1221242110
更新日期:2013-06-04 00:00:00
abstract::We have isolated a human gastrin gene from a genomic library by employing a human gastrin cDNA clone as a hybridization probe. The total length of the gene is approximately 4.0 kilobase pairs, and the gene is separated into three exons and two introns. A 130-base-pair intron interrupts the coding region and a 3.0-kilo...
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.81.15.4662
更新日期:1984-08-01 00:00:00