Bacterial TANGO2 homologs are heme-trafficking proteins that facilitate biosynthesis of cytochromes c

作者：Sirui Han, Kailun Guo, Wei Wang, Yizhi Jane Tao, Haichun Gao · 发表于：mBio · 年份：2023 · DOI：10.1128/mbio.01320-23 · 被引用次数：17 · 研究领域：Photosynthetic Processes and Mechanisms、Porphyrin Metabolism and Disorders、Microbial Fuel Cells and Bioremediation

ABSTRACT Heme, an essential molecule for virtually all living organisms, acts primarily as a cofactor in a large number of proteins. However, how heme is mobilized from the site of synthesis to the locations where hemoproteins are assembled remains largely unknown in cells, especially bacterial ones. In this study, with Shewanella oneidensis as the model, we identified HtpA (SO0126) as a heme-trafficking protein and homolog of TANGO2 proteins found in eukaryotes. We showed that HtpA homologs are widely distributed in all domains of living organisms and have undergone parallel evolution. In its absence, the cytochrome (cyt) c content and catalase activity decreased significantly. We further showed that both HtpA and representative TANGO2 proteins bind heme with 1:1 stoichiometry and a relatively low dissociation constant. Protein interaction analyses substantiated that HtpA directly interacts with the cytochrome c maturation system. Our findings shed light on cross-membrane transport of heme in bacteria and extend the understanding of TANGO2 proteins. IMPORTANCE The intracellular trafficking of heme, an essential cofactor for hemoproteins, remains underexplored even in eukaryotes, let alone bacteria. Here we developed a high-throughput method by which HtpA, a homolog of eukaryotic TANGO2 proteins, was identified to be a heme-binding protein that enhances cytochrome c biosynthesis and catalase activity in Shewanella oneidensis . HtpA interacts with the cytochrome c biosynthesis...