title: A heme-based redox sensor in the methanogenic archaeon Methanosarcina acetivorans.
abstract: Based on a bioinformatics study, the protein MA4561 from the methanogenic archaeon Methanosarcina acetivorans was originally predicted to be a multidomain phytochrome-like photosensory kinase possibly binding open-chain tetrapyrroles. Although we were able to show that recombinantly produced and purified protein does not bind any known phytochrome chromophores, UV-visible spectroscopy revealed the presence of a heme tetrapyrrole cofactor. In contrast to many other known cytoplasmic heme-containing proteins, the heme was covalently attached via one vinyl side chain to cysteine 656 in the second GAF domain. This GAF domain by itself is sufficient for covalent attachment. Resonance Raman and magnetic circular dichroism data support a model of a six-coordinate heme species with additional features of a five-coordination structure. The heme cofactor is redox-active and able to coordinate various ligands like imidazole, dimethyl sulfide, and carbon monoxide depending on the redox state. Interestingly, the redox state of the heme cofactor has a substantial influence on autophosphorylation activity. Although reduced protein does not autophosphorylate, oxidized protein gives a strong autophosphorylation signal independent from bound external ligands. Based on its genomic localization, MA4561 is most likely a sensor kinase of a two-component system effecting regulation of the Mts system, a set of three homologous corrinoid/methyltransferase fusion protein isoforms involved in methyl sulfide metabolism. Consistent with this prediction, an M. acetivorans mutant devoid of MA4561 constitutively synthesized MtsF. On the basis of our results, we postulate a heme-based redox/dimethyl sulfide sensory function of MA4561 and propose to designate it MsmS (methyl sulfide methyltransferase-associated sensor).
authors: Physiology of Microorganisms, Faculty of Biology and Biotechnology, Ruhr University Bochum, Universitaetsstrasse 150, 44780 Bochum, Germany.
authors: Bastian
authors: B
authors: Molitor
authors: Marc
authors: M
authors: Stassen
authors: Anuja
authors: A
authors: Modi
authors: Samir F
authors: SF
authors: El-Mashtoly
authors: Christoph
authors: C
authors: Laurich
authors: Wolfgang
authors: W
authors: Lubitz
authors: John H
authors: JH
authors: Dawson
authors: Michael
authors: M
authors: Rother
authors: Nicole
authors: N
authors: Frankenberg-Dinkel
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D008697:Methane / Q000378:metabolism*; D017020:Methanosarcina / Q000235:genetics / Q000378:metabolism*; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D010084:Oxidation-Reduction; D010766:Phosphorylation; D010770:Phosphotransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013059:Spectrum Analysis, Raman; D013440:Sulfides / Q000737:chemistry / Q000378:metabolism
chemical_list: D019843:Archaeal Proteins; D013440:Sulfides; D006418:Heme; D008780:Methyltransferases; D010770:Phosphotransferases; D011494:Protein Kinases; D008697:Methane; C004784:dimethyl sulfide
keywords: Archaea; Heme; Methanosarcina; Raman Spectroscopy; Redox Signaling; Sensor Kinase; Signal Transduction; UV Spectroscopy
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