Accelerated evolution of a minimal 63-amino acid dual transcription factor.

Abstract:

:Transcription factors control gene expression in all life. This raises the question of what is the smallest protein that can support such activity. In nature, Cro from bacteriophage λ is one of the smallest known repressors (66 amino acids), and activators are typically much larger (e.g., λ cI, 237 amino acids). Previous efforts to engineer a minimal activator from λ Cro resulted in no activity in vivo in cells. In this study, we show that directed evolution results in a new Cro activator-repressor that functions as efficiently as λ cI in vivo. To achieve this, we develop phagemid-assisted continuous evolution (PACEmid). We find that a peptide as small as 63 amino acids functions efficiently as an activator and/or repressor. To our knowledge, this is the smallest protein activator that enables polymerase recruitment, highlighting the capacity of transcription factors to evolve from very short peptide sequences.

journal_name

Sci Adv

journal_title

Science advances

authors

Brödel AK,Rodrigues R,Jaramillo A,Isalan M

doi

10.1126/sciadv.aba2728

subject

Has Abstract

pub_date

2020-06-10 00:00:00

pages

eaba2728

issue

24

issn

2375-2548

pii

aba2728

journal_volume

6

pub_type

杂志文章
  • pH-dependent gating mechanism of the Helicobacter pylori urea channel revealed by cryo-EM.

    abstract::The urea channel of Helicobacterpylori (HpUreI) is an ideal drug target for preventing gastric cancer but incomplete understanding of its gating mechanism has hampered development of inhibitors for the eradication of H. pylori. Here, we present the cryo-EM structures of HpUreI in closed and open conformations, both at...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aav8423

    authors: Cui Y,Zhou K,Strugatsky D,Wen Y,Sachs G,Zhou ZH,Munson K

    更新日期:2019-03-20 00:00:00

  • Self-luminescent photodynamic therapy using breast cancer targeted proteins.

    abstract::Despite the potential of photodynamic therapy (PDT), its comprehensive use in cancer treatment has not been achieved because of the nondegradable risks of photosensitizing drugs and limits of light penetration and instrumentation. Here, we present bioluminescence (BL)-induced proteinaceous PDT (BLiP-PDT), through the ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aba3009

    authors: Kim EH,Park S,Kim YK,Moon M,Park J,Lee KJ,Lee S,Kim YP

    更新日期:2020-09-11 00:00:00

  • Semiconductor glass with superior flexibility and high room temperature thermoelectric performance.

    abstract::Most crystalline inorganic materials, except for metals and some layer materials, exhibit bad flexibility because of strong ionic or covalent bonds, while amorphous materials usually display poor electrical properties due to structural disorders. Here, we report the simultaneous realization of extraordinary room tempe...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaz8423

    authors: He S,Li Y,Liu L,Jiang Y,Feng J,Zhu W,Zhang J,Dong Z,Deng Y,Luo J,Zhang W,Chen G

    更新日期:2020-04-10 00:00:00

  • Compositional mantle layering revealed by slab stagnation at ~1000-km depth.

    abstract::Improved constraints on lower-mantle composition are fundamental to understand the accretion, differentiation, and thermochemical evolution of our planet. Cosmochemical arguments indicate that lower-mantle rocks may be enriched in Si relative to upper-mantle pyrolite, whereas seismic tomography images suggest whole-ma...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1500815

    authors: Ballmer MD,Schmerr NC,Nakagawa T,Ritsema J

    更新日期:2015-12-10 00:00:00

  • Three-dimensional graphene/Pt nanoparticle composites as freestanding anode for enhancing performance of microbial fuel cells.

    abstract::Microbial fuel cells (MFCs) are able to directly convert about 50 to 90% of energy from oxidation of organic matters in waste to electricity and have great potential application in broad fields such as wastewater treatment. Unfortunately, the power density of the MFCs at present is significantly lower than the theoret...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1500372

    authors: Zhao S,Li Y,Yin H,Liu Z,Luan E,Zhao F,Tang Z,Liu S

    更新日期:2015-11-13 00:00:00

  • Sequence-encoded colloidal origami and microbot assemblies from patchy magnetic cubes.

    abstract::Colloidal-scale assemblies that reconfigure on demand may serve as the next generation of soft "microbots," artificial muscles, and other biomimetic devices. This requires the precise arrangement of particles into structures that are preprogrammed to reversibly change shape when actuated by external fields. The design...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1701108

    authors: Han K,Shields CW 4th,Diwakar NM,Bharti B,López GP,Velev OD

    更新日期:2017-08-04 00:00:00

  • Saigas on the brink: Multidisciplinary analysis of the factors influencing mass mortality events.

    abstract::In 2015, more than 200,000 saiga antelopes died in 3 weeks in central Kazakhstan. The proximate cause of death is confirmed as hemorrhagic septicemia caused by the bacterium Pasteurella multocida type B, based on multiple strands of evidence. Statistical modeling suggests that there was unusually high relative humidit...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aao2314

    authors: Kock RA,Orynbayev M,Robinson S,Zuther S,Singh NJ,Beauvais W,Morgan ER,Kerimbayev A,Khomenko S,Martineau HM,Rystaeva R,Omarova Z,Wolfs S,Hawotte F,Radoux J,Milner-Gulland EJ

    更新日期:2018-01-17 00:00:00

  • Structure and mechanism of bactericidal mammalian perforin-2, an ancient agent of innate immunity.

    abstract::Perforin-2 (MPEG1) is thought to enable the killing of invading microbes engulfed by macrophages and other phagocytes, forming pores in their membranes. Loss of perforin-2 renders individual phagocytes and whole organisms significantly more susceptible to bacterial pathogens. Here, we reveal the mechanism of perforin-...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aax8286

    authors: Ni T,Jiao F,Yu X,Aden S,Ginger L,Williams SI,Bai F,Pražák V,Karia D,Stansfeld P,Zhang P,Munson G,Anderluh G,Scheuring S,Gilbert RJC

    更新日期:2020-01-29 00:00:00

  • Confinement-induced self-organization in growing bacterial colonies.

    abstract::We investigate the emergence of global alignment in colonies of dividing rod-shaped cells under confinement. Using molecular dynamics simulations and continuous modeling, we demonstrate that geometrical anisotropies in the confining environment give rise to an imbalance in the normal stresses, which, in turn, drives a...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abc8685

    authors: You Z,Pearce DJG,Giomi L

    更新日期:2021-01-22 00:00:00

  • Increasing the revenue from lignocellulosic biomass: Maximizing feedstock utilization.

    abstract::The production of renewable chemicals and biofuels must be cost- and performance- competitive with petroleum-derived equivalents to be widely accepted by markets and society. We propose a biomass conversion strategy that maximizes the conversion of lignocellulosic biomass (up to 80% of the biomass to useful products) ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1603301

    authors: Alonso DM,Hakim SH,Zhou S,Won W,Hosseinaei O,Tao J,Garcia-Negron V,Motagamwala AH,Mellmer MA,Huang K,Houtman CJ,Labbé N,Harper DP,Maravelias C,Runge T,Dumesic JA

    更新日期:2017-05-19 00:00:00

  • Strong-coupling ansatz for the one-dimensional Fermi gas in a harmonic potential.

    abstract::A major challenge in modern physics is to accurately describe strongly interacting quantum many-body systems. One-dimensional systems provide fundamental insights because they are often amenable to exact methods. However, no exact solution is known for the experimentally relevant case of external confinement. We propo...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1500197

    authors: Levinsen J,Massignan P,Bruun GM,Parish MM

    更新日期:2015-07-24 00:00:00

  • Agriculture is a major source of NO x pollution in California.

    abstract::Nitrogen oxides (NO x = NO + NO2) are a primary component of air pollution-a leading cause of premature death in humans and biodiversity declines worldwide. Although regulatory policies in California have successfully limited transportation sources of NO ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aao3477

    authors: Almaraz M,Bai E,Wang C,Trousdell J,Conley S,Faloona I,Houlton BZ

    更新日期:2018-01-31 00:00:00

  • Systemic inequalities for LGBTQ professionals in STEM.

    abstract::Researchers have documented race and gender inequality in science, technology, engineering, and math (STEM) for decades. Do lesbian, gay, bisexual, transgender, and queer (LGBTQ) professionals face parallel experiences of disadvantage in STEM? Using representative survey data from 21 STEM professional societies (Nsamp...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abe0933

    authors: Cech EA,Waidzunas TJ

    更新日期:2021-01-15 00:00:00

  • Parallel PRC2/cPRC1 and vPRC1 pathways silence lineage-specific genes and maintain self-renewal in mouse embryonic stem cells.

    abstract::The transcriptional repressors Polycomb repressive complex 1 (PRC1) and PRC2 are required to maintain cell fate during embryonic development. PRC1 and PRC2 catalyze distinct histone modifications, establishing repressive chromatin at shared targets. How PRC1, which consists of canonical PRC1 (cPRC1) and variant PRC1 (...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aax5692

    authors: Zepeda-Martinez JA,Pribitzer C,Wang J,Bsteh D,Golumbeanu S,Zhao Q,Burkard TR,Reichholf B,Rhie SK,Jude J,Moussa HF,Zuber J,Bell O

    更新日期:2020-04-01 00:00:00

  • Direct quantitative measurement of the C═O⋅⋅⋅H-C bond by atomic force microscopy.

    abstract::The hydrogen atom-the smallest and most abundant atom-is of utmost importance in physics and chemistry. Although many analysis methods have been applied to its study, direct observation of hydrogen atoms in a single molecule remains largely unexplored. We use atomic force microscopy (AFM) to resolve the outermost hydr...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1603258

    authors: Kawai S,Nishiuchi T,Kodama T,Spijker P,Pawlak R,Meier T,Tracey J,Kubo T,Meyer E,Foster AS

    更新日期:2017-05-12 00:00:00

  • Twist again: Dynamically and reversibly controllable chirality in liquid crystalline elastomer microposts.

    abstract::Photoresponsive liquid crystalline elastomers (LCEs) constitute ideal actuators for soft robots because their light-induced macroscopic shape changes can be harnessed to perform specific articulated motions. Conventional LCEs, however, do not typically exhibit complex modes of bending and twisting necessary to perform...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay5349

    authors: Waters JT,Li S,Yao Y,Lerch MM,Aizenberg M,Aizenberg J,Balazs AC

    更新日期:2020-03-27 00:00:00

  • Regulation of energy rheostasis by the melanocortin-3 receptor.

    abstract::Like most homeostatic systems, adiposity in mammals is defended between upper and lower boundary conditions. While leptin and melanocortin-4 receptor (MC4R) signaling are required for defending energy set point, mechanisms controlling upper and lower homeostatic boundaries are less well understood. In contrast to the ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aat0866

    authors: Ghamari-Langroudi M,Cakir I,Lippert RN,Sweeney P,Litt MJ,Ellacott KLJ,Cone RD

    更新日期:2018-08-22 00:00:00

  • Mass spectrometry imaging identifies abnormally elevated brain l-DOPA levels and extrastriatal monoaminergic dysregulation in l-DOPA-induced dyskinesia.

    abstract::l-DOPA treatment for Parkinson's disease frequently leads to dyskinesias, the pathophysiology of which is poorly understood. We used MALDI-MSI to map the distribution of l-DOPA and monoaminergic pathways in brains of dyskinetic and nondyskinetic primates. We report elevated levels of l-DOPA, and its metabolite 3-O-met...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abe5948

    authors: Fridjonsdottir E,Shariatgorji R,Nilsson A,Vallianatou T,Odell LR,Schembri LS,Svenningsson P,Fernagut PO,Crossman AR,Bezard E,Andrén PE

    更新日期:2021-01-06 00:00:00

  • Range of motion in the avian wing is strongly associated with flight behavior and body mass.

    abstract::Avian wing shape is highly variable across species but only coarsely associated with flight behavior, performance, and body mass. An underexplored but potentially explanatory feature is the ability of birds to actively change wing shape to meet aerodynamic and behavioral demands. Across 61 species, we found strong ass...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaw6670

    authors: Baliga VB,Szabo I,Altshuler DL

    更新日期:2019-10-23 00:00:00

  • Bioinspired oral delivery of gut microbiota by self-coating with biofilms.

    abstract::Transplanting beneficial bacteria to the gut microbiome can positively modulate the bacterial composition and remains of great interest in prevention and treatment. However, environmental assaults and rapid transit times in the gastrointestinal (GI) tract result in low oral bioavailability and limited intestinal colon...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abb1952

    authors: Wang X,Cao Z,Zhang M,Meng L,Ming Z,Liu J

    更新日期:2020-06-24 00:00:00

  • Human endogenous retroviral protein triggers deficit in glutamate synapse maturation and behaviors associated with psychosis.

    abstract::Mobile genetic elements, such as human endogenous retroviruses (HERVs), produce proteins that regulate brain cell functions and synaptic transmission and have been implicated in the etiology of neurological and neurodevelopmental psychiatric disorders. However, the mechanisms by which these proteins of retroviral orig...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.abc0708

    authors: Johansson EM,Bouchet D,Tamouza R,Ellul P,Morr AS,Avignone E,Germi R,Leboyer M,Perron H,Groc L

    更新日期:2020-07-17 00:00:00

  • A kinase bioscavenger provides antibiotic resistance by extremely tight substrate binding.

    abstract::Microbial communities are self-controlled by repertoires of lethal agents, the antibiotics. In their turn, these antibiotics are regulated by bioscavengers that are selected in the course of evolution. Kinase-mediated phosphorylation represents one of the general strategies for the emergence of antibiotic resistance. ...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaz9861

    authors: Terekhov SS,Mokrushina YA,Nazarov AS,Zlobin A,Zalevsky A,Bourenkov G,Golovin A,Belogurov A Jr,Osterman IA,Kulikova AA,Mitkevich VA,Lou HJ,Turk BE,Wilmanns M,Smirnov IV,Altman S,Gabibov AG

    更新日期:2020-06-24 00:00:00

  • A pressure-induced topological phase with large Berry curvature in Pb1-x Sn x Te.

    abstract::The picture of how a gap closes in a semiconductor has been radically transformed by topological concepts. Instead of the gap closing and immediately reopening, topological arguments predict that, in the absence of inversion symmetry, a metallic phase protected by Weyl nodes persists over a finite interval of the tuni...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1602510

    authors: Liang T,Kushwaha S,Kim J,Gibson Q,Lin J,Kioussis N,Cava RJ,Ong NP

    更新日期:2017-05-31 00:00:00

  • Super-resolution nanoscopy by coherent control on nanoparticle emission.

    abstract::Super-resolution nanoscopy based on wide-field microscopic imaging provided high efficiency but limited resolution. Here, we demonstrate a general strategy to push its resolution down to ~50 nm, which is close to the range of single molecular localization microscopy, without sacrificing the wide-field imaging advantag...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaw6579

    authors: Liu C,Liu W,Wang S,Li H,Lv Z,Zhang F,Zhang D,Teng J,Zheng T,Li D,Zhang M,Xu P,Gong Q

    更新日期:2020-04-17 00:00:00

  • The key player problem in complex oscillator networks and electric power grids: Resistance centralities identify local vulnerabilities.

    abstract::Identifying key players in coupled individual systems is a fundamental problem in network theory. We investigate synchronizable network-coupled dynamical systems such as high-voltage electric power grids and coupled oscillators on complex networks. We define key players as nodes that, once perturbed, generate the larg...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaw8359

    authors: Tyloo M,Pagnier L,Jacquod P

    更新日期:2019-11-22 00:00:00

  • The immunoproteasome catalytic β5i subunit regulates cardiac hypertrophy by targeting the autophagy protein ATG5 for degradation.

    abstract::Pathological cardiac hypertrophy eventually leads to heart failure without adequate treatment. The immunoproteasome is an inducible form of the proteasome that is intimately involved in inflammatory diseases. Here, we found that the expression and activity of immunoproteasome catalytic subunit β5i were significantly u...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aau0495

    authors: Xie X,Bi HL,Lai S,Zhang YL,Li N,Cao HJ,Han L,Wang HX,Li HH

    更新日期:2019-05-08 00:00:00

  • Probing the chemistry of CdS paints in The Scream by in situ noninvasive spectroscopies and synchrotron radiation x-ray techniques.

    abstract::The degradation of cadmium sulfide (CdS)-based oil paints is a phenomenon potentially threatening the iconic painting The Scream (ca. 1910) by Edvard Munch (Munch Museum, Oslo) that is still poorly understood. Here, we provide evidence for the presence of cadmium sulfate and sulfites as alteration products of the orig...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aay3514

    authors: Monico L,Cartechini L,Rosi F,Chieli A,Grazia C,De Meyer S,Nuyts G,Vanmeert F,Janssens K,Cotte M,De Nolf W,Falkenberg G,Sandu ICA,Tveit ES,Mass J,de Freitas RP,Romani A,Miliani C

    更新日期:2020-05-15 00:00:00

  • PPM1A silences cytosolic RNA sensing and antiviral defense through direct dephosphorylation of MAVS and TBK1.

    abstract::Cytosolic RNA sensing is a prerequisite for initiation of innate immune response against RNA viral pathogens. Signaling through RIG-I (retinoic acid-inducible gene I)-like receptors (RLRs) to TBK1 (Tank-binding kinase 1)/IKKε (IκB kinase ε) kinases is transduced by mitochondria-associated MAVS (mitochondrial antiviral...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.1501889

    authors: Xiang W,Zhang Q,Lin X,Wu S,Zhou Y,Meng F,Fan Y,Shen T,Xiao M,Xia Z,Zou J,Feng XH,Xu P

    更新日期:2016-07-01 00:00:00

  • Motion tracking of 80-nm-size skyrmions upon directional current injections.

    abstract::Nanometer-scale skyrmions are prospective candidates for information bits in low-power consumption devices owing to their topological nature and controllability with low current density. Studies on skyrmion dynamics in different classes of materials have exploited the topological Hall effect and current-driven fast mo...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aaz9744

    authors: Yu XZ,Morikawa D,Nakajima K,Shibata K,Kanazawa N,Arima T,Nagaosa N,Tokura Y

    更新日期:2020-06-17 00:00:00

  • IRONSperm: Sperm-templated soft magnetic microrobots.

    abstract::We develop biohybrid magnetic microrobots by electrostatic self-assembly of nonmotile sperm cells and magnetic nanoparticles. Incorporating a biological entity into microrobots entails many functional advantages beyond shape templating, such as the facile uptake of chemotherapeutic agents to achieve targeted drug deli...

    journal_title:Science advances

    pub_type: 杂志文章

    doi:10.1126/sciadv.aba5855

    authors: Magdanz V,Khalil ISM,Simmchen J,Furtado GP,Mohanty S,Gebauer J,Xu H,Klingner A,Aziz A,Medina-Sánchez M,Schmidt OG,Misra S

    更新日期:2020-07-08 00:00:00