Stabilizing synapsis

June 18th, 2018 by Yiyun Song

Stabilizing synapsis

Stabilizing synapsis, Published online: 18 June 2018; doi:10.1038/s41589-018-0095-3

Stabilizing synapsis

[ASAP] Charge Dispersion and Its Effects on the Reactivity of Thiamin-Derived Breslow Intermediates

June 14th, 2018 by Michael Bielecki, Graeme W. Howe, Ronald Kluger

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.8b00463

The RNA-binding complex ESCRT-II in Xenopus laevis eggs recognizes purine-rich sequences through its subunit Vps25 [Cell Biology]

June 14th, 2018 by Amy B Emerman, Michael Blower

RNA-binding proteins (RBPs) are critical regulators of gene expression. Recent studies have uncovered hundreds of mRNA-binding proteins that do not contain annotated RNA-binding domains and have well-established roles in other cellular processes. Investigation of these nonconventional RBPs is critical for revealing novel RNA-binding domains and may disclose connections between RNA regulation and other aspects of cell biology. Endosomal sorting complex required for transport II (ESCRT-II) is a nonconventional RNA-binding complex that has a canonical role in multivesicular body formation. ESCRT-II previously has been identified as an RNA-binding complex in Drosophila oocytes, but whether its RNA-binding properties extend beyond Drosophila is unknown. In this study, we found that the RNA-binding properties of ESCRT-II are conserved in Xenopus eggs, where ESCRT-II interacted with hundreds of mRNAs. Using a UV-crosslinking approach, we demonstrated that ESCRT-II binds directly to RNA through its subunit Vps25. UV-crosslinking and immunoprecipitation (CLIP)-Seq revealed that Vps25 specifically recognizes a polypurine (i.e. GA-rich) motif in RNA. Using purified components, we could reconstitute the selective Vps25-mediated binding of the polypurine motif in vitro. Our results provide insight into the mechanism by which ESCRT-II selectively binds to mRNAs and also suggest an unexpected link between endosome biology and RNA regulation.

Plasticity in binding confers selectivity in ligand-induced protein degradation

June 11th, 2018 by Radosław P. Nowak

Plasticity in binding confers selectivity in ligand-induced protein degradation

Plasticity in binding confers selectivity in ligand-induced protein degradation, Published online: 11 June 2018; doi:10.1038/s41589-018-0055-y

Selectivity of ligand-induced protein degradation and dimerization is conferred by plastic interprotein contacts. Computational protein–protein docking reveals the underlying interprotein contacts to inform the design of a BRD4 selective degrader.
  • Posted in Nat Chem Biol, Publications
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Linkers for protein degradation

June 11th, 2018 by Philip P. Chamberlain

Linkers for protein degradation

Linkers for protein degradation, Published online: 11 June 2018; doi:10.1038/s41589-018-0057-9

The ability to subvert E3 ubiquitin ligases with small-molecule drugs offers tremendous promise for drug discovery. A new study demonstrates how structural and computational techniques can engineer and exploit unnatural protein–protein interfaces to design selective protein degraders.

Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern

June 11th, 2018 by Benoit Castrec

Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern

Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern, Published online: 11 June 2018; doi:10.1038/s41589-018-0077-5

Aided by the solving of the structures of human NMT1 with substrate-mimicking peptides, mapping of human and Arabidopsis myristoylomes defines a myristoylation recognition motif and over 1,000 myristoylated protein targets.
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Functional assignment of multiple catabolic pathways for <span class=”small-caps”>d</span>-apiose

June 4th, 2018 by Michael S. Carter

Functional assignment of multiple catabolic pathways for d-apiose

Functional assignment of multiple catabolic pathways for <span class="small-caps">d</span>-apiose, Published online: 04 June 2018; doi:10.1038/s41589-018-0067-7

A bioinformatic strategy beginning with solute-binding proteins involved in sugar transport led to the functional annotation of four previously unknown catabolic pathways of the branched pentose d-apiose.
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Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins

June 4th, 2018 by Jianchao Li

Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins

Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins, Published online: 04 June 2018; doi:10.1038/s41589-018-0082-8

Potent pan-Atg8 or GABARAP-selective inhibitory peptides derived from giant neuronal ankyrin-B and -G effectively block autophagy in cell cultures and in C. elegans spatiotemporally.
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Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme

June 4th, 2018 by Nan Wang

Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme

Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme, Published online: 04 June 2018; doi:10.1038/s41589-018-0061-0

Functional and structural characterization of PtmA2 reveals that it is an unusual non-adenylating acyl-CoA ligase and part of a system wherein the canonical acyl-CoA ligase reaction is separated into two half-reactions performed by distinct enzymes.
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Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system

June 4th, 2018 by Tong Xiao

Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system

Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system, Published online: 04 June 2018; doi:10.1038/s41589-018-0062-z

Copper contributes to regulating zebrafish rest–activity cycles through the locus coeruleus system by modulating the biosynthesis of norepinephrine; brain copper deficiency leads to lower levels of both synaptic norepinephrine and daytime activity.
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