Iron Transport Proteins: Gateways of Cellular and Systemic Iron Homeostasis [Cell Biology]

June 16th, 2017 by Mitchell D. Knutson

Cellular iron homeostasis is maintained by iron and heme transport proteins that work in concert with ferrireductases, ferroxidases, and chaperones to direct the movement of iron into, within, and out of cells. Systemic iron homeostasis is regulated by the liver-derived peptide hormone, hepcidin. The interface between cellular and systemic iron homeostasis is readily observed in the highly dynamic iron handling of four main cell types: duodenal enterocytes, erythrocyte precursors, macrophages, and hepatocytes. This review provides an overview of how these cell types handle iron, highlighting how iron and heme transporters mediate the exchange and distribution of body iron in health and disease.

A ciliary opsin in the brain of a marine annelid zooplankton is UV-sensitive and the sensitivity is tuned by a single amino acid residue [Molecular Biophysics]

June 16th, 2017 by Hisao Tsukamoto, I-Shan Chen, Yoshihiro Kubo, Yuji Furutani

Ciliary opsins were classically thought to function only in vertebrates for vision, but they have been recently identified also in invertebrates for non-visual photoreception. Larvae of the annelid Platynereis dumerilii are used as a zooplankton model, and this zooplankton species possesses a "vertebrate-type" ciliary opsin (named c-opsin) in the brain. Platynereis c-opsin is suggested to relay light signals to melatonin production and circadian behaviors. Thus, the spectral and biochemical characteristics of this c-opsin would be directly related to non-visual photoreception in this zooplankton model. Here, we demonstrate that the c-opsin can sense UV to activate intracellular signaling cascades, and that it can directly bind exogenous all-trans-retinal. These results suggest that this c-opsin regulates circadian signaling in a UV-dependent manner and that it does not require supply of 11-cis-retinal for photoreception. Avoidance of damaging UV irradiation is a major cause of a large-scale daily zooplankton movement, and the observed capability of the c-opsin to transmit UV signals and bind all-trans-retinal is ideally suited for sensing UV radiation in the brain, which presumably lacks enzymes producing 11-cis-retinal. Mutagenesis analyses indicated that a unique amino acid residue (Lys-94) is responsible for c-opsin-mediated UV sensing in the Platynereis brain. We therefore propose that acquisition of the lysine residue in the c-opsin would be a critical event in the evolution of Platynereis to enable detection of ambient UV. In summary, our findings indicate that the c-opsin possesses spectral and biochemical properties suitable for UV sensing by the zooplankton model.
  • Posted in Journal of Biological Chemistry, Publications
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Two Dynamical Regimes of the Substrate Radical Rearrangement Reaction in B12-Dependent Ethanolamine Ammonia-Lyase Resolve Contributions of Native Protein Configurations and Collective Configurational Fluctuations to Catalysis

June 15th, 2017 by Meghan Kohne, Chen Zhu and Kurt Warncke

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.7b00294

Oxidation of phosphorothioate DNA modifications leads to lethal genomic instability

June 12th, 2017 by Stefanie Kellner

Nature Chemical Biology 13, 888 (2017). doi:10.1038/nchembio.2407

Authors: Stefanie Kellner, Michael S DeMott, Ching Pin Cheng, Brandon S Russell, Bo Cao, Delin You & Peter C Dedon

  • Posted in Nat Chem Biol, Publications
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Genetically encoding phosphotyrosine and its nonhydrolyzable analog in bacteria

June 12th, 2017 by Xiaozhou Luo

Nature Chemical Biology 13, 845 (2017). doi:10.1038/nchembio.2405

Authors: Xiaozhou Luo, Guangsen Fu, Rongsheng E Wang, Xueyong Zhu, Claudio Zambaldo, Renhe Liu, Tao Liu, Xiaoxuan Lyu, Jintang Du, Weimin Xuan, Anzhi Yao, Sean A Reed, Mingchao Kang, Yuhan Zhang, Hui Guo, Chunhui Huang, Peng-Yu Yang, Ian A Wilson, Peter G Schultz & Feng Wang

  • Posted in Nat Chem Biol, Publications
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A mutant O-GlcNAcase enriches Drosophila developmental regulators

June 12th, 2017 by Nithya Selvan

Nature Chemical Biology 13, 882 (2017). doi:10.1038/nchembio.2404

Authors: Nithya Selvan, Ritchie Williamson, Daniel Mariappa, David G Campbell, Robert Gourlay, Andrew T Ferenbach, Tonia Aristotelous, Iva Hopkins-Navratilova, Matthias Trost & Daan M F van Aalten

A front-face ‘SNi synthase’ engineered from a retaining ‘double-SN2’ hydrolase

June 12th, 2017 by Javier Iglesias-Fernández

Nature Chemical Biology 13, 874 (2017). doi:10.1038/nchembio.2394

Authors: Javier Iglesias-Fernández, Susan M Hancock, Seung Seo Lee, Maola Khan, Jo Kirkpatrick, Neil J Oldham, Katherine McAuley, Anthony Fordham-Skelton, Carme Rovira & Benjamin G Davis

  • Posted in Nat Chem Biol, Publications
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A scalable platform to identify fungal secondary metabolites and their gene clusters

June 12th, 2017 by Kenneth D Clevenger

Nature Chemical Biology 13, 895 (2017). doi:10.1038/nchembio.2408

Authors: Kenneth D Clevenger, Jin Woo Bok, Rosa Ye, Galen P Miley, Maria H Verdan, Thomas Velk, Cynthia Chen, KaHoua Yang, Matthew T Robey, Peng Gao, Matthew Lamprecht, Paul M Thomas, Md Nurul Islam, Jonathan M Palmer, Chengcang C Wu, Nancy P Keller & Neil L Kelleher

  • Posted in Nat Chem Biol, Publications
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Site-specific incorporation of phosphotyrosine using an expanded genetic code

June 12th, 2017 by Christian Hoppmann

Nature Chemical Biology 13, 842 (2017). doi:10.1038/nchembio.2406

Authors: Christian Hoppmann, Allison Wong, Bing Yang, Shuwei Li, Tony Hunter, Kevan M Shokat & Lei Wang

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination.

  • Posted in Nat Chem Biol, Publications
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Activity-based probes for functional interrogation of retaining β-glucuronidases

June 5th, 2017 by Liang Wu

Nature Chemical Biology 13, 867 (2017). doi:10.1038/nchembio.2395

Authors: Liang Wu, Jianbing Jiang, Yi Jin, Wouter W Kallemeijn, Chi-Lin Kuo, Marta Artola, Wei Dai, Cas van Elk, Marco van Eijk, Gijsbert A van der Marel, Jeroen D C Codée, Bogdan I Florea, Johannes M F G Aerts, Herman S Overkleeft & Gideon J Davies

  • Posted in Nat Chem Biol, Publications
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