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.
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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

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Biochemistry
DOI: 10.1021/acs.biochem.7b00294

Remote Perturbations in Tertiary Contacts Trigger Ligation of Lysine to the Heme Iron in Cytochrome c

May 31st, 2017 by Jie Gu, Dong-Woo Shin and Ekaterina V. Pletneva

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Biochemistry
DOI: 10.1021/acs.biochem.6b01187

Call for Nominations for 2017-2018 ACS Division of Biological Chemistry Awards

May 30th, 2017 by pthomas2

Nominations are requested for the Eli Lilly Award in Biological Chemistry, the Pfizer Award in Enzyme Chemistry, and the Repligen Award in Chemistry of Biological Processes in addition to the Gordon Hammes Biochemistry Lectureship, the ACS Chemical Biology Lectureship and the Murray Goodman Memorial Prize, please visit the Nominations page for more information.

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Deamidation Slows Curli Amyloid-Protein Aggregation

May 26th, 2017 by Hanliu Wang, Qin Shu, Carl Frieden and Michael L. Gross

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Biochemistry
DOI: 10.1021/acs.biochem.7b00241

Endoplasmic Reticulum Stress-induced Degradation of DNAJB12 Stimulates BOK Accumulation and Primes Cancer Cells for Apoptosis [Cell Biology]

May 23rd, 2017 by Pattarawut Sopha, Hong Yu Ren, Diane E. Grove, Douglas M Cyr

DNAJB12 (JB12) is an endoplasmic reticulum (ER)-associated Hsp40 family protein that recruits Hsp70 to the ER surface to coordinate the function of ER-associated and cytosolic chaperone systems in protein quality control. Hsp70 is stress inducible, but paradoxically, we report here that JB12 was degraded by the proteasome during severe ER stress. Destabilized JB12 was degraded by ER-associated degradation (ERAD) complexes that contained HERP, Sel1L, and gp78. JB12 was the only ER-associated chaperone that was destabilized by reductive stress. JB12 knockdown by siRNA led to the induction of Caspase processing, but not the unfolded protein response. ER stress-induced apoptosis is regulated by the highly labile and ER associated BCL-2 family member BOK, which is controlled at the level of protein stability by ERAD components. We found that JB12 was required in Huh-7 liver cancer cells to maintain BOK at low levels and BOK was detected in complexes with JB12 and gp78. Depletion of JB12 during reductive stress or by shRNA from Huh-7 cells was associated with accumulation of BOK, and activation of Caspase 3, 7, and 9. Absence of JB12 sensitized Huh-7 to death caused by proteotoxic agents and the proapoptotic chemotherapeutic LCL-161. In summary, JB12 is a stress sensitive Hsp40 whose degradation during severe ER stress provides a mechanism to promote BOK accumulation and induction of apoptosis.

Celiac Disease: Lessons for and from Chemical Biology

May 22nd, 2017 by Chaitan Khosla

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ACS Chemical Biology
DOI: 10.1021/acschembio.6b01155

Induced Fit Is a Special Case of Conformational Selection

May 22nd, 2017 by Pradipta Chakraborty and Enrico Di Cera

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Biochemistry
DOI: 10.1021/acs.biochem.7b00340

The sialate O-acetylesterase EstA from gut Bacteroidetes species enables sialidase-mediated cross-species foraging of 9-O-acetylated sialoglycans [Microbiology]

May 19th, 2017 by Lloyd S Robinson, Warren G Lewis, Amanda L Lewis

The gut harbors many symbiotic, commensal, and pathogenic microbes that engage in the breakdown and metabolism of host carbohydrates. Sialic acids are prominent outermost carbohydrates on mucins and protect underlying glycan chains from enzymatic degradation. Sialidases produced by some members of the colonic microbiota have been shown to promote the expansion of several potential pathogens (e.g. Clostridium difficile, Salmonella, Escherichia coli) that do not produce sialidases. O-acetyl ester modifications of sialic acids help resist the action of many sialidases and are found at high levels in the mammalian colon. However, some gut bacteria, in turn, produce sialylate-O-acetyl esterases to remove them. Here we investigated O-acetylation as a shield against the release of sialic acids by Bacteroidetes sialidases and the subsequent utilization of host sialic acids by commensal and pathogenic strains of E. coli. In vitro foraging studies demonstrated that sialidase-dependent E. coli outgrowth on mucin is enabled by Bacteroides EstA, which acts on glycosidically-linked sialylate-O-acety-esterase substrates, particularly at neutral pH. Biochemical studies suggest that spontaneous migration of O-acetyl esters on the side chain of sialic acid, which can occur at colonic pH, may serve as a switch controlling EstA-assisted sialic acid liberation. Specifically, EstA does not act on O-acetyl esters in their initial 7-position. But, following migration to the 9-position, glycans with O-acetyl esters become susceptible to the sequential enzyme action of bacterial esterases and sialidases. Thus, EstA specifically unlocks the nutritive potential of 9-O-acetylated mucus sialic acids for foraging by bacteria that otherwise lack the means to access this potential carbon source.
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