Abstract：
:Due to regulatory feedback, biological networks can exist stably in multiple states, leading to heterogeneous phenotypes among genetically identical cells. Random fluctuations in protein numbers, tuned by specific molecular mechanisms, have been hypothesized to drive transitions between these different states. We develop a minimal theoretical framework to analyze the limits of switching in terms of simple experimental parameters. Our model identifies and distinguishes between two distinct molecular mechanisms for generating stochastic switches. In one class of switches, the stochasticity of a single-molecule event, a specific and rare molecular reaction, directly controls the macroscopic change in a cell's state. In the second class, no individual molecular event is significant, and stochasticity arises from the propagation of biochemical noise through many molecular pathways and steps. As an example, we explore switches based on protein-DNA binding fluctuations and predict relations between transcription factor kinetics, absolute switching rate, robustness, and efficiency that differentiate between switching by single-molecule events or many molecular steps. Finally, we apply our methods to recent experimental data on switching in Escherichia coli lactose metabolism, providing quantitative interpretations of a single-molecule switching mechanism.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Choi PJ,Xie XS,Shakhnovich EIdoi
10.1016/j.jmb.2009.11.035subject
Has Abstractpub_date
2010-02-12 00:00:00pages
230-44issue
1eissn
0022-2836issn
1089-8638pii
S0022-2836(09)01412-0journal_volume
396pub_type
杂志文章abstract：:The X-ray structures of two hemoglobins (Hb) from the sea cucumber Caudina arenicola (an echinoderm) have been determined: a low spin, hemichrome, monomeric Hb-C chain, and a cyanomet-liganded dimeric Hb-D chain. Attempts to obtain crystal structures of the deoxy-liganded and hemichrome forms from the same chain type ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1995.0445
更新日期：1995-08-18 00:00:00
abstract：:The effects of RNA methylation on HIV-1 replication remain largely unknown. Recent studies have discovered new insights into the effect of 2'-O-methylation and 5-methylcytidine marks on the HIV-1 RNA genome. As so far, HIV-1 benefits from diverse RNA methylations through distinct mechanisms. In this review, we summari...
journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(85)90285-2
更新日期：1985-05-05 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(89)90566-4
更新日期：1989-04-20 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1996.0553
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2001.5312
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journal_title：Journal of molecular biology
pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1016/j.jmb.2008.04.076
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journal_title：Journal of molecular biology
pub_type： 杂志文章
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.11.029
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journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
doi：10.1016/j.jmb.2016.03.021
更新日期：2016-08-14 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2005.05.016
更新日期：2005-07-22 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2004.11.001
更新日期：2005-01-28 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1994.0011
更新日期：1995-01-13 00:00:00
abstract：:Crystals have been obtained of threonyl-tRNA synthetase from the extreme thermophile Thermus thermophilus using sodium formate as a precipitant. The crystals are very stable and diffract to at least 2.4 A. The crystals belong to space group P2(1)2(1)2(1) with cell parameters a = 61.4 A, b = 156.1 A, c = 177.3 A. ...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(90)90337-L
更新日期：1990-08-20 00:00:00
abstract：:We have studied in reconstitution experiments the conditions under which peptides derived from histones H1 and H5 are bound in chromatin and to what extent they are involved in the organization of chromatin fibers. The fragments of rat liver histone H1 (rH1) and chicken erythrocytes H1 (cH1) and H5 (cH5) used were the...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/s0022-2836(83)80102-8
更新日期：1983-07-05 00:00:00
abstract：:The replacement of cis proline 39 of ribonuclease T1 by an alanine residue leads to a decrease in stability by about 20 kJ/mol and to major changes in the folding kinetics that are not easily explained by the proline model for protein folding. In particular, a novel very slow reaction is observed in the refolding of t...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1993.1337
更新日期：1993-06-05 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/S0022-2836(05)80096-8
更新日期：1990-09-05 00:00:00
abstract：:Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease affecting cattle that is transmissible to humans, manifesting as a variant of Creutzfeldt-Jakob disease (vCJD) likely following the consumption of meat contaminated with BSE prions. High-affinity antibodies are a prerequisite for the dev...
journal_title：Journal of molecular biology
pub_type： 杂志文章
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journal_title：Journal of molecular biology
pub_type： 杂志文章
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.4252
更新日期：2000-12-15 00:00:00
abstract：:The effect of GT/CA dinucleotide repeat tracts on RecA-dependent homologous recombination was examined in vitro. By measuring the binding of RecA protein to oligonucleotides containing GT or CA repeats using the surface plasmon resonance (BIAcore), we show that the efficiency of RecA protein binding is sequence depend...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1997.1293
更新日期：1997-10-17 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章,评审
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abstract：:The tetracycline analog 9-(N, N-dimethylglycylamido)-6-demethyl-6-deoxy-tetracycline (9glyTc) belongs to a new group of tetracyclines called glycylcyclines. They are strong antibiotics showing reduced sensitivity against the major tetracycline resistance mechanisms. We have determined the crystal structure of 9glyTc i...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.1998.2290
更新日期：1999-01-15 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2006.06.011
更新日期：2006-07-28 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2008.12.018
更新日期：2009-02-13 00:00:00
abstract：:Fasciculin 2 and toxin alpha proteins belong to the same structural family of three-fingered snake toxins. They act on different targets, but in each case the binding region involves residues from loops I and II. The superimposition of the two structures suggests that these functional regions correspond to structurall...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1006/jmbi.2000.3510
更新日期：2000-03-03 00:00:00
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journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2019.12.047
更新日期：2020-02-14 00:00:00
abstract：:The Rad1-Rad9-Hus1 (9-1-1) complex serves a dual role as a DNA-damage sensor in checkpoint signaling and as a mediator in the DNA repair pathway. However, the intercellular mechanisms that regulate the 9-1-1 complex are poorly understood. Jab1, the fifth component of the COP9 signalosome complex, has a central role in...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/j.jmb.2007.05.095
更新日期：2007-08-10 00:00:00
abstract：:The vicinal amide proton-C alpha proton spin-spin coupling constants, JHN alpha, in the globular protein basic pancreatic trypsin inhibitor (BPTI) have been measured using phase-sensitive correlated spectroscopy at high digital resolution. In conjunction with the crystal structure of BPTI, these data were used to cali...
journal_title：Journal of molecular biology
pub_type： 杂志文章
doi：10.1016/0022-2836(84)90035-4
更新日期：1984-12-15 00:00:00
