Small heat shock proteins: Simplicity meets complexity [Cell Biology]

October 31st, 2018 by Martin Haslbeck, Sevil Weinkauf, Johannes Buchner

Small heat shock proteins (sHsps) are a ubiquitous and ancient family of ATP-independent molecular chaperones. A key characteristic of sHsps is that they exist in ensembles of iso-energetic oligomeric species differing in size. This property arises from a unique mode of assembly involving several parts of the subunits in a flexible manner. Current evidence suggests that smaller oligomers are more active chaperones. Thus, a shift in the equilibrium of the sHsp ensemble allows regulating the chaperone activity. Different mechanisms have been identified that reversibly change the oligomer equilibrium. The promiscuous interaction with non-native proteins generates complexes that can form aggregate-like structures from which native proteins are restored by ATP-dependent chaperones such as Hsp70 family members. In recent years, this basic paradigm has been expanded and new roles, new cofactors as well as variations in structure and regulation of sHsps have emerged.

[ASAP] Precise Small Molecule Degradation of a Noncoding RNA Identifies Cellular Binding Sites and Modulates an Oncogenic Phenotype

October 29th, 2018 by Yue Li, Matthew D. Disney

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ACS Chemical Biology
DOI: 10.1021/acschembio.8b00827
  • Posted in ACS Chemical Biology, Publications
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Identification of a cellularly active SIRT6 allosteric activator

October 29th, 2018 by Zhimin Huang

Identification of a cellularly active SIRT6 allosteric activator

Identification of a cellularly active SIRT6 allosteric activator, Published online: 29 October 2018; doi:10.1038/s41589-018-0150-0

The use of an allosteric drug-design method resulted in the identification of a first-in-class cellularly active SIRT6 activator that induces cell-cycle arrest in the G0–G1 phase, thus suppressing proliferation in human hepatocellular carcinoma cells.

Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking

October 29th, 2018 by Xin Li

Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking

Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking, Published online: 29 October 2018; doi:10.1038/s41589-018-0144-y

An inhibitor of the YEATS domain was developed by targeting a unique π-π-π stacking in the YEATS–Kcr recognition. An ENL YEATS-selective inhibitor, XL-13m, helps probe the YEATS-dependent role of ENL in the leukemogenic transcription program.
  • Posted in Nat Chem Biol, Publications
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The multicatalytic compartment of propionyl-CoA synthase sequesters a toxic metabolite

October 29th, 2018 by Iria Bernhardsgrütter

The multicatalytic compartment of propionyl-CoA synthase sequesters a toxic metabolite

The multicatalytic compartment of propionyl-CoA synthase sequesters a toxic metabolite, Published online: 29 October 2018; doi:10.1038/s41589-018-0153-x

Structural and biochemical analysis of propionyl-CoA synthase reveals that it forms a reaction chamber containing three active sites, which sequesters the reactive intermediate acrylyl-CoA during the conversion of 3-hydroxypropionate to propionyl-CoA.
  • Posted in Nat Chem Biol, Publications
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[ASAP] Retroelement-Based Genome Editing and Evolution

October 25th, 2018 by Anna J. Simon, Barrett R. Morrow, Andrew D. Ellington

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ACS Synthetic Biology
DOI: 10.1021/acssynbio.8b00273

[ASAP] Transcription Driven by Reversible Photocontrol of Hyperstable G-Quadruplexes

October 16th, 2018 by Shinzi Ogasawara

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ACS Synthetic Biology
DOI: 10.1021/acssynbio.8b00216

Chaperoning partners

October 16th, 2018 by Grant Miura

Chaperoning partners

Chaperoning partners, Published online: 16 October 2018; doi:10.1038/s41589-018-0157-6

Chaperoning partners

Metabolic repair through emergence of new pathways in <i>Escherichia coli</i>

October 16th, 2018 by Sammy Pontrelli

Metabolic repair through emergence of new pathways in Escherichia coli

Metabolic repair through emergence of new pathways in <i>Escherichia coli</i>, Published online: 16 October 2018; doi:10.1038/s41589-018-0149-6

In response to the deletion of key genes involved in biosynthesis of the essential CoA precursor β-alanine, Escherichia coli overcomes this pathway damage by successively evolving alternative metabolic pathways.
  • Posted in Nat Chem Biol, Publications
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A new spot for PKR

October 16th, 2018 by Yiyun Song

A new spot for PKR

A new spot for PKR, Published online: 16 October 2018; doi:10.1038/s41589-018-0159-4

A new spot for PKR