ACS DIVISION OF BIOLOGICAL CHEMISTRY

November 25th, 2019 by William B. Black

Nature Chemical Biology, Published online: 25 November 2019; doi:10.1038/s41589-019-0402-7

Redesign of a glucose dehydrogenase to use nicotinamide mononucleotide (NMN+) instead of NAD(P)+ enables the development of a noncanonical cofactor system that can be used to support redox chemistries both in vitro and in Escherichia coli.

November 25th, 2019 by Pauli S. Losoi*, Ville P. Santala, and Suvi M. Santala

November 25th, 2019 by

November 22nd, 2019 by Henry D Galvin, Matloob Husain

Influenza A virus (IAV) effectively manipulates host machinery to replicate. There is a growing evidence that an optimal acetylation environment in the host cell is favourable to IAV proliferation and vice versa. The histone deacetylases (HDACs) – a family of 18 host enzymes classified into four classes, are central to negatively regulating the acetylation level, hence the HDACs would not be favourable to IAV. Indeed, by using the RNA interference and overexpression strategies, we found that human HDAC4 – a class II member, possesses anti-IAV properties and is a component of host innate antiviral response. We discovered that IAV multiplication was augmented in HDAC4-depleted cells and abated in HDAC4-supplemented cells. Likewise, the expression of IFITM3, ISG15, and viperin – some of the critical markers of host anti-IAV response was abated in HDAC4-depleted cells and augmented in HDAC4-supplemented cells. In turn, IAV strongly antagonises the HDAC4, by downregulating its expression both at mRNA level via viral RNA endonuclease PA-X and at polypeptide level by inducing its cleavage via host caspase 3 in infected cells. Such HDAC4 polypeptide cleavage resulted in a ~30 kDa fragment which is also observed in some heterologous systems and may have a significant role in IAV replication.

November 22nd, 2019 by Mark W. Ruszczycky*† and Hung-wen Liu†‡

November 21st, 2019 by Jiantao Zhang, Yanmei Hu, Nan Wu, and Jun Wang*

November 20th, 2019 by Yuichi Sekine, Jane A. Lindborg, Stephen M. Strittmatter

Glial signals are known to inhibit axonal regeneration and functional recovery after mammalian central nervous system (CNS) trauma, including spinal cord injury. Such signals include membrane-associated proteins of the oligodendrocyte plasma membrane and astrocyte-derived matrix-associated proteins. Here, using cell lines and primary cortical neuron cultures, recombinant protein expression, immunoprecipitation and immunoblotting assays, transmission EM of exosomes, and axon-regeneration assays, we explored the secretion and activity of the myelin-associated, neurite outgrowth inhibitor Nogo-A and observed exosomal release of a 24-kDa, C-terminal Nogo-A fragment from cultured cells. We found that the cleavage site in this 1192-amino-acid-long fragment is located between amino acids 961–971. We also detected a Nogo-66 receptor (NgR1)-interacting Nogo-66 domain on the exosome surface. Enzyme inhibitor treatment and siRNA knockdown revealed that β-secretase 1 (BACE1) is the protease responsible for the Nogo-A cleavage. Functionally, exosomes with the Nogo-66 domain on their surface potently inhibited axonal regeneration of mechanically injured cerebral cortex neurons from mice. The production of this fragment was observed in the exosomal fraction from neuronal tissue lysates after spinal cord crush injury of mice. We also noted that relative to the exosomal marker Alix, a Nogo-immunoreactive 24-kDa protein is enriched in exosomes two-fold after injury. We conclude that membrane-associated Nogo-A produced in oligodendrocytes is processed proteolytically by BACE1, is released via exosomes, and represents a potent diffusible inhibitor of regenerative growth in NgR1-expressing axons.

November 18th, 2019 by Zhenrun J. Zhang

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0392-5

Microbiota-derived butyrate acylation of the key Salmonella enterica transcriptional regulator HilA attenuates virulence of the bacteria, blocking invasion of epithelial cells in vitro and dissemination in vivo.

November 18th, 2019 by Marcus Conrad

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0408-1

This Perspective focuses on the chemical basis of ferroptotic cell death, discussing the prominent role of spontaneous chemical reactions, how they depend on enzyme-catalyzed processes and how to exploit this interplay for therapeutic benefit.

November 18th, 2019 by Takashi Yokogawa

Nature Chemical Biology, Published online: 18 November 2019; doi:10.1038/s41589-019-0390-7

Euryarchaeal ArcS alone cannot produce G+-containing tRNA but works as a lysine transferase to produce a lysine adduct intermediate, which finally forms G+-containing tRNA in the presence of a newly identified SAM enzyme, RaSEA.