Abstract:
:The overall structure of the transition-state and intermediate ensembles observed experimentally for dihydrofolate reductase and interleukin-1beta can be obtained by using simplified models that have almost no energetic frustration. The predictive power of these models suggests that, even for these very large proteins with completely different folding mechanisms and functions, real protein sequences are sufficiently well designed, and much of the structural heterogeneity observed in the intermediates and the transition-state ensembles is determined by topological effects.
journal_name
Proc Natl Acad Sci U S Aauthors
Clementi C,Jennings PA,Onuchic JNdoi
10.1073/pnas.100547897keywords:
subject
Has Abstractpub_date
2000-05-23 00:00:00pages
5871-6issue
11eissn
0027-8424issn
1091-6490pii
100547897journal_volume
97pub_type
杂志文章abstract::Previously metal-ion sites have been used as structural and functional probes in seven transmembrane receptors (7TM), but as yet all the engineered sites have been inactivating. Based on presumed agonist interaction points in transmembrane III (TM-III) and -VII of the beta(2)-adrenergic receptor, in this paper we cons...
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.96.22.12322
更新日期:1999-10-26 00:00:00
abstract::Bacteriophage T7 encodes an essential inhibitor of the Escherichia coli host RNA polymerase (RNAP), the product of gene 2 (Gp2). We determined a series of X-ray crystal structures of E. coli RNAP holoenzyme with or without Gp2. The results define the structure and location of the RNAP σ(70) subunit domain 1.1(σ(1.1)(7...
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.1314576110
更新日期:2013-12-03 00:00:00
abstract::Environmental and anthropogenic factors often drive population declines in top predators, but how their influences may combine remains unclear. Albatrosses are particularly threatened. They breed in fast-changing environments, and their extensive foraging ranges expose them to incidental mortality (bycatch) in multipl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2017-12-12 00:00:00
abstract::The DNA end-joining protein Ku70 is one of several proteins that inhibit apoptosis by sequestering the proapoptotic factor Bax from the mitochondria. However, the molecular mechanism underlying Ku70-dependent inhibition of Bax is not fully understood. Here, we show that the absence of Ku70 results in the accumulation ...
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.0706700105
更新日期:2008-04-01 00:00:00
abstract::Diverse motivations for preserving nature both inspire and hinder its conservation. Optimal conservation strategies may differ radically depending on the objective. For example, creating nature reserves may prevent extinctions through protecting severely threatened species, whereas incentivizing farmland hedgerows may...
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.1504788112
更新日期:2015-09-01 00:00:00
abstract::Transforming growth factor (TGF)-beta plays a pivotal role in regulation of progression of cancer through effects on tumor microenvironment as well as on cancer cells. TGF-beta inhibitors have recently been shown to prevent the growth and metastasis of certain cancers. However, there may be adverse effects caused by T...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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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
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更新日期:2004-07-27 00:00:00
abstract::We have recently demonstrated that immunization with hepatitis C virus-like particles (HCV-LPs) generated in insect cells can elicit both humoral and cellular immune responses in BALB/c mice. Here, we evaluate the immunogenicity of HCV-LPs in HLA2.1 transgenic (AAD) mice in comparison to DNA immunization. HCV-LP immun...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2003-05-27 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2006-02-14 00:00:00
abstract::Phosphatidylinositol 4,5-bisphosphate (PIP2) is an important cellular effector whose functions include the regulation of ion channels and membrane trafficking. Aberrant PIP2 metabolism has also been implicated in a variety of human disease states, e.g., cancer and diabetes. Here we report that familial Alzheimer's dis...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2006-12-19 00:00:00
abstract::Many neurodegenerative diseases are characterized by the accumulation of amyloid fibers in the brain, which can occur when a protein misfolds into an extended beta-sheet conformation. The nucleation of these beta-sheet aggregates is of particular interest, not only because it is the rate-determining step toward fiber ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2005-10-04 00:00:00
abstract::Rapid North Atlantic cooling events during the last deglaciation caused atmospheric reorganizations on global and regional scales. Their impact on Asian climate has been investigated for monsoonal domains, but remains largely unknown in westerly wind-dominated semiarid regions. Here we generate a dust record from sout...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2020-08-04 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.1109728109
更新日期:2012-05-15 00:00:00
abstract::Local levels of active thyroid hormone (3,3',5-triiodothyronine) are controlled by the action of activating and inactivating iodothyronine deiodinase enzymes. Deiodinases are selenocysteine-dependent membrane proteins catalyzing the reductive elimination of iodide from iodothyronines through a poorly understood mechan...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2014-07-22 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.91.25.12317
更新日期:1994-12-06 00:00:00
abstract::The FKBP12-rapamycin-associated protein (FRAP; also called RAFT1/mTOR) regulates translation initiation and entry into the cell cycle. Depriving cells of amino acids or treating them with the small molecule rapamycin inhibits FRAP and results in rapid dephosphorylation and inactivation of the translational regulators ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:1999-04-13 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2002-01-08 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2019-10-08 00:00:00
abstract::The adrenergic receptors (ARs) (subtypes alpha 1, alpha 2, beta 1, and beta 2) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. We have previously assigned the genes for ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::The interaction between the ribosomal-stalk protein L7/12 (L12) and initiation factor 2 (IF2) is essential for rapid subunit association, but the underlying mechanism is unknown. Here, we have characterized the L12-IF2 interaction on Escherichia coli ribosomes using site-directed mutagenesis, fast kinetics, and molecu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2018-05-01 00:00:00
abstract::G protein-coupled receptors (GPCRs) have been found as monomers but also as dimers or higher-order oligomers in cells. The relevance of the monomeric or dimeric receptor state for G protein activation is currently under debate for class A rhodopsin-like GPCRs. Clarification of this issue requires the availability of w...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2007-07-17 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.81.4.1208
更新日期:1984-02-01 00:00:00
abstract::Veratridine or high potassium concentration increased guanosine 3',5'-cyclic monophosphate (cGMP) levels in neuroblastoma cells of clone N1E-115 without affecting levels of adenosine 3',5'-cyclic monophosphate (cAMP). The increases in cGMP appear to be a direct result of the depolarizing action of these agents and not...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1978-12-01 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.1220341110
更新日期:2013-03-05 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2016-09-20 00:00:00
abstract::Three-dimensional microfluidic systems were fabricated and used to pattern proteins and mammalian cells on a planar substrate. The three-dimensional topology of the microfluidic network in the stamp makes this technique a versatile one with which to pattern multiple types of proteins and cells in complex, discontinuou...
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.040562297
更新日期:2000-03-14 00:00:00