Abstract:
:Conditional cooperativity is a common mechanism involved in transcriptional regulation of prokaryotic type II toxin-antitoxin operons and is intricately related to bacterial persistence. It allows the toxin component of a toxin-antitoxin module to act as a co-repressor at low doses of toxin as compared to antitoxin. When toxin level exceeds a certain threshold, however, the toxin becomes a de-repressor. Most antitoxins contain an intrinsically disordered region (IDR) that typically is involved in toxin neutralization and repressor complex formation. To address how the antitoxin IDR is involved in transcription regulation, we studied the phd-doc operon from bacteriophage P1. We provide evidence that the IDR of Phd provides an entropic barrier precluding full operon repression in the absence of Doc. Binding of Doc results in a cooperativity switch and consequent strong operon repression, enabling context-specific modulation of the regulatory process. Variations of this theme are likely to be a common mechanism in the autoregulation of bacterial operons that involve intrinsically disordered regions.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Garcia-Pino A,De Gieter S,Talavera A,De Greve H,Efremov RG,Loris Rdoi
10.1038/nchembio.2078subject
Has Abstractpub_date
2016-07-01 00:00:00pages
490-6issue
7eissn
1552-4450issn
1552-4469pii
nchembio.2078journal_volume
12pub_type
杂志文章abstract:: ...
journal_title:Nature chemical biology
pub_type: 评论,杂志文章
doi:10.1038/s41589-019-0230-9
更新日期:2019-03-01 00:00:00
abstract::BCL-2 family protein interactions regulate apoptosis, a critical process that maintains tissue homeostasis but can cause a host of human diseases when deregulated. Venetoclax is the first FDA-approved drug to reactivate apoptosis in cancer by selectively targeting an anti-apoptotic BCL-2 family member. The drug's acti...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/s41589-019-0306-6
更新日期:2019-07-01 00:00:00
abstract::Oxidase and oxygenase enzymes allow the use of relatively unreactive O2 in biochemical reactions. Many of the mechanistic strategies used in nature for this key reaction are represented within the 2-histidine-1-carboxylate facial triad family of non-heme Fe(II)-containing enzymes. The open face of the metal coordinati...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.71
更新日期:2008-03-01 00:00:00
abstract::RNA capping and decapping are thought to be distinctive features of eukaryotes. The redox cofactor NAD was recently discovered to be attached to small regulatory RNAs in bacteria in a cap-like manner, and Nudix hydrolase NudC was found to act as a NAD-decapping enzyme in vitro and in vivo. Here, crystal structures of ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2132
更新日期:2016-09-01 00:00:00
abstract::The catalytic activity of many protein kinases is controlled by conformational changes of a conserved Asp-Phe-Gly (DFG) motif. We used an infrared probe to track the DFG motif of the mitotic kinase Aurora A (AurA) and found that allosteric activation by the spindle-associated protein Tpx2 involves an equilibrium shift...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2296
更新日期:2017-04-01 00:00:00
abstract::Small molecules that specifically activate an intracellular protein of interest are highly desirable. A generally applicable strategy, however, remains elusive. Herein we describe a small molecule-triggered bioorthogonal protein decaging technique that relies on the inverse electron-demand Diels-Alder reaction for eli...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1656
更新日期:2014-12-01 00:00:00
abstract::Antibody-drug conjugates (ADCs) selectively deliver chemotherapeutic agents to target cells and are important cancer therapeutics. However, the mechanisms by which ADCs are internalized and activated remain unclear. Using CRISPR-Cas9 screens, we uncover many known and novel endolysosomal regulators as modulators of AD...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0342-2
更新日期:2019-10-01 00:00:00
abstract::Subtilosin A is a 35-residue, ribosomally synthesized bacteriocin encoded by the sbo-alb operon of Bacillus subtilis. It is composed of a head-to-tail circular peptide backbone that is additionally restrained by three unusual thioether bonds between three cysteines and the α-carbon of one threonine and two phenylalani...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.798
更新日期:2012-02-26 00:00:00
abstract::Cell-permeable small molecules that inhibit their targets on fast timescales are powerful probes of cell-division mechanisms. Such inhibitors have been identified using phenotype-based screens with chemical libraries. However, the characteristics of compound libraries needed to effectively span cell-division phenotype...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio826
更新日期:2006-11-01 00:00:00
abstract::The plant hormone auxin regulates virtually every aspect of plant growth and development. Auxin acts by binding the F-box protein transport inhibitor response 1 (TIR1) and promotes the degradation of the AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) transcriptional repressors. Here we show that efficient auxin binding requires...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.926
更新日期:2012-04-01 00:00:00
abstract::CRISPR-Cas9 has emerged as a powerful technology that enables ready modification of the mammalian genome. The ability to modulate Cas9 activity can reduce off-target cleavage and facilitate precise genome engineering. Here we report the development of a Cas9 variant whose activity can be switched on and off in human c...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2179
更新日期:2016-11-01 00:00:00
abstract::Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2251
更新日期:2017-02-01 00:00:00
abstract::Nature is a diverse and rich source of bioactive pathways or novel building blocks for synthetic biology. In this Perspective, we describe the emerging research field in which metagenomes are functionally interrogated using synthetic biology. This approach substantially expands the set of identified biological activit...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/s41589-018-0100-x
更新日期:2018-08-01 00:00:00
abstract::Drug discovery resources in academia and industry are not used efficiently, to the detriment of industry and society. Duplication could be reduced, and productivity could be increased, by performing basic biology and clinical proofs of concept within open access industry-academia partnerships. Chemical biologists coul...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio0709-436
更新日期:2009-07-01 00:00:00
abstract::Transient receptor potential (TRP) proteins form plasma-membrane cation channels that act as sensors for diverse cellular stimuli. Here, we report a novel activation mechanism mediated by cysteine S-nitrosylation in TRP channels. Recombinant TRPC1, TRPC4, TRPC5, TRPV1, TRPV3 and TRPV4 of the TRPC and TRPV families, wh...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio821
更新日期:2006-11-01 00:00:00
abstract::Serine phosphorylation is a key post-translational modification that regulates diverse biological processes. Powerful analytical methods have identified thousands of phosphorylation sites, but many of their functions remain to be deciphered. A key to understanding the function of protein phosphorylation is access to p...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1823
更新日期:2015-07-01 00:00:00
abstract::Despite the fundamental roles of sialyl- and fucosyltransferases in mammalian physiology, there are few pharmacological tools to manipulate their function in a cellular setting. Although fluorinated analogs of the donor substrates are well-established transition state inhibitors of these enzymes, they are not membrane...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.999
更新日期:2012-07-01 00:00:00
abstract::We report that simple glycoside donors can drastically shift the equilibria of glycosyltransferase-catalyzed reactions, transforming NDP-sugar formation from an endothermic to an exothermic process. To demonstrate the utility of this thermodynamic adaptability, we highlight the glycosyltransferase-catalyzed synthesis ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.638
更新日期:2011-08-21 00:00:00
abstract::Learning regulatory networks from genomics data is an important problem with applications spanning all of biology and biomedicine. Functional genomics projects offer a cost-effective means of greatly expanding the completeness of our regulatory models, and for some prokaryotic organisms they offer a means of learning ...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.122
更新日期:2008-11-01 00:00:00
abstract::Trafficking and sorting of membrane-anchored Ras GTPases are regulated by partitioning between distinct membrane domains. Here, in vitro experiments and microscopic molecular theory reveal membrane curvature as a new modulator of N-Ras lipid anchor and palmitoyl chain partitioning. Membrane curvature was essential for...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1733
更新日期:2015-03-01 00:00:00
abstract::Identification of endogenous glycan-binding ligands for cell-surface receptors has been difficult. Incorporation of a photoactive sialic acid analog into B-cell surface glycoproteins suggests that CD22 molecules may cluster by binding carbohydrate antigens on neighboring CD22 molecules. ...
journal_title:Nature chemical biology
pub_type: 评论,新闻
doi:10.1038/nchembio0705-69
更新日期:2005-07-01 00:00:00
abstract::The GATOR1 (SEACIT) complex consisting of Iml1-Npr2-Npr3 inhibits target of rapamycin complex 1 (TORC1) in response to amino acid insufficiency. In glucose medium, Saccharomyces cerevisiae mutants lacking the function of this complex grow poorly in the absence of amino acid supplementation, despite showing hallmarks o...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2478
更新日期:2017-11-01 00:00:00
abstract::We describe a new technology for recruiting specific proteins to RNA through selective recognition of heteroduplexes formed with chemically modified antisense oligonucleotides (ASOs). Typically, ASOs function by hybridizing to their RNA targets and blocking the binding of single-stranded RNA-binding proteins. Unexpect...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.939
更新日期:2012-04-15 00:00:00
abstract::Accumulation of unfolded proteins within the endoplasmic reticulum (ER) of eukaryotic cells leads to an unfolded protein response (UPR) that either restores homeostasis or commits the cells to apoptosis. Tools traditionally used to study the UPR are proapoptotic and thus confound analysis of long-term cellular respons...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1638
更新日期:2014-11-01 00:00:00
abstract::Nontranslational functions of vertebrate aminoacyl tRNA synthetases (aaRSs), which catalyze the production of aminoacyl-tRNAs for protein synthesis, have recently been discovered. Although these new functions were thought to be 'moonlighting activities', many are as critical for cellular homeostasis as their activity ...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.1158
更新日期:2013-03-01 00:00:00
abstract::Bioinorganic chemistry remains a vibrant discipline at the interface of chemistry and the biological sciences. Metal ions function in numerous metalloenzymes, are incorporated into pharmaceuticals and imaging agents, and inspire the synthesis of catalysts used to achieve many chemical transformations. ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio1006-504
更新日期:2006-10-01 00:00:00
abstract::The heat shock protein 90 (Hsp90) has a critical role in malignant transformation. Whereas its ability to maintain the functional conformations of mutant and aberrant oncoproteins is established, a transformation-specific regulation of the antiapoptotic phenotype by Hsp90 is poorly understood. By using selective compo...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2007.10
更新日期:2007-08-01 00:00:00
abstract::Combination antiretroviral therapy has transformed HIV-1 infection, once a fatal illness, into a manageable chronic condition. Drug resistance, severe side effects and treatment noncompliance bring challenges to combination antiretroviral therapy implementation in clinical settings and indicate the need for additional...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-0496-y
更新日期:2020-05-01 00:00:00
abstract::The P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, bu...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1863
更新日期:2015-09-01 00:00:00
abstract::The eukaryotic 26S proteasome controls cellular processes by degrading specific regulatory proteins. Most proteins are targeted for degradation by a signal or degron that consists of two parts: a proteasome-binding tag, typically covalently attached polyubiquitin chains, and an unstructured region that serves as the i...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.521
更新日期:2011-03-01 00:00:00