With many crucial roles in enzymatic aerobic metabolism, the concentration of the heme must be tightly regulated. The heme exporter Feline Leukemia Virus sub-group C Receptor 1a (FLVCR1a), an integral membrane protein with twelve transmembrane helices, is a key player in the maintenance of cellular heme homeostasis. It was first identified as the host receptor for the Feline Leukemia Virus sub-group C (FeLV-C), a retrovirus causing hematological abnormalities in cats and other felines. Mutations in the Flvcr1 were later identified in human patients affected by Posterior Column Ataxia and Retinitis Pigmentosa (PCARP) and Hereditary Sensory and Autonomic Neuropathies (HSANs). Despite being an essential component in heme balance, currently there is a lack in the understanding of its function at the molecular level, including the effect of disease-causing mutations on protein function and structure. Therefore, there is a need for protocols to achieve efficient recombinant production yielding milligram amounts of highly pure protein to be used for biochemical and structural studies. Here, we report the first FLVCR1a reliable protocol suitable for both antibody generation and structural characterisation.
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http://dx.doi.org/10.1016/j.pep.2020.105637 | DOI Listing |
J Clin Invest
December 2024
State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer.
The cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway is a critical driver of type I interferon (IFN-I) and antitumor CD8+ T cell responses after radiotherapy (RT). In this issue of the JCI, two reports describe mechanisms that restrained STING signaling and abrogated antitumor immunity after RT. Wen, Wang, and colleagues discovered that IFN-I mediated the induction of YTHDF1, an RNA N6-methyladenosine-binding protein, in DCs after RT promoted cathepsin-mediated STING degradation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
Univ. Lille, CNRS, INSERM, Centre Hospitalier Universitaire de Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - Center for Infection and Immunity of Lille, Lille F-59000, France.
Ribosomally synthesized and posttranslationally modified peptides (RiPPs) are a structurally diverse group of natural products that bacteria employ in their survival strategies. Herein, we characterized the structure, the biosynthetic pathway, and the mode of action of a RiPP family called bufferins. With thousands of homologous biosynthetic gene clusters throughout the bacterial phylogenetic tree, bufferins form by far the largest family of RiPPs modified by multinuclear nonheme iron-dependent oxidases (MNIO, DUF692 family).
View Article and Find Full Text PDFFront Cell Infect Microbiol
November 2024
Membrane Protein Structural Biology Group, Center for Structural Systems Biology (CSSB), Hamburg, Germany.
Host iron deficiency is protective against severe malaria as the human malaria parasite depends on bioavailable iron from its host to proliferate. The essential pathways of iron acquisition, storage, export, and detoxification in the parasite differ from those in humans, as orthologs of the mammalian transferrin receptor, ferritin, or ferroportin, and a functional heme oxygenase are absent in . Thus, the proteins involved in these processes may be excellent targets for therapeutic development, yet remain largely unknown.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2024
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112.
malaria parasites invade and multiply inside red blood cells (RBCs), the most iron-rich compartment in humans. Like all cells, requires nutritional iron to support essential metabolic pathways, but the critical mechanisms of iron acquisition and trafficking during RBC infection have remained obscure. Parasites internalize and liberate massive amounts of heme during large-scale digestion of RBC hemoglobin within an acidic food vacuole (FV) but lack a heme oxygenase to release porphyrin-bound iron.
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