Structure, function and evolution of the hemerythrin‐like domain superfamily

Álvarez-Carreño, Claudia; Alva, Vikram; Becerra, Arturo; Lazcano, Antonio

doi:10.1002/pro.3374

Cited by 39 publications

(51 citation statements)

References 54 publications

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“…native proteins are comprised of six or eight of these subunits [8,9] although a bacterial hemerythrin has been identified that is a monomer [10]. The other HLPs with different iron ligation patterns and different biological functions possess additional domains on each protein that are required for their respective biological functions.…”

Section: Discussionmentioning

confidence: 99%

“…These proteins typically are comprised of identical subunits of four α-helices, with each subunit housing a di-iron site with a bridging oxygen. The proteins typically possess six or eight of these subunits [8,9], although monomeric hemerythrins have been identified in the bacterium Methylococcus capsulatus [10] and the peanut worm Themiste hennahi [11]. The recombinant Rv2633c protein that was expressed in Escherichia coli and purified [7] was a homodimer that contained two iron ions per subunit.…”

Section: Introductionmentioning

confidence: 99%

“…The nature of the additional domain confers distinct biological functions, which often relate to signal transduction via methyl-accepting chemotaxis, diguanylate cyclase, or adenlyl cyclase domains [12]. The ligation pattern of the di-iron site also varies with function among these HLPs, both in the number and identity of the amino acid residues that provide ligands for the two iron ions [9]. Other HLPs include an oxygen-sensing protein from Desulfovibrio vulgaris [13], an iron sensing protein in humans [14], and the YtfE protein from E. coli [15].…”

Section: Introductionmentioning

confidence: 99%

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Crystal structure of a hemerythrin-like protein from Mycobacterium kansasii and homology model of the orthologous Rv2633c protein of M. tuberculosis

Abendroth

Buchko

et al. 2020

Biochemical Journal

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Pathogenic and opportunistic mycobacteria have a distinct class of non-heme di-iron hemerythrin-like proteins (HLPs). The first to be isolated was the Rv2633c protein, which plays a role in infection by Mycobacterium tuberculosis (Mtb), but could not be crystallized. This work presents the first crystal structure of an ortholog of Rv2633c, the mycobacterial HLP from Mycobacterium kansasii (Mka). This structure differs from those of hemerythrins and other known HLPs. It consists of five α-helices, whereas all other HLP domains have four. In contrast with other HLPs, the HLP domain is not fused to an additional protein domain. The residues ligating and surrounding the di-iron site are also unique among HLPs. Notably, a tyrosine occupies the position normally held by one of the histidine ligands in hemerythrin. This structure was used to construct a homology model of Rv2633c. The structure of five α-helices is conserved and the di-iron site ligands are identical in Rv2633c. Two residues near the ends of helices in the Mka HLP structure are replaced with prolines in the Rv2633c model. This may account for structural perturbations that decrease the solubility of Rv2633c relative to Mka HLP. Clusters of residues that differ in charge or polarity between Rv2633c and Mka HLP that point outward from the helical core could reflect a specificity for potential differential interactions with other protein partners in vivo, which are related to function. The Mka HLP exhibited weaker catalase activity than Rv2633c. Evidence was obtained for the interaction of Mka HLP irons with nitric oxide.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Crystal structure of a hemerythrin-like protein from Mycobacterium kansasii and homology model of the orthologous Rv2633c protein of M. tuberculosis

Abendroth

Buchko

et al. 2020

Biochemical Journal

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“…Hemerythrin-like proteins are also found in bacteria, archaea and some eukaryotic groups including humans; however, their functions are not clear. They are proposed to be oxygen or iron sensors, oxygen carriers, or to act as protectors under oxidative stress conditions ( Alvarez-Carreño et al, 2018 ). Also, among the proteins that were considerably upregulated under excessive copper we found two homologs of a heme-containing protein, protoglobin.…”

Section: Discussionmentioning

confidence: 99%

Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system

Grechnikova

Ženíšková

Malych

et al. 2020

International Journal for Parasitology: Drugs and Drug Resistan

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Copper is a trace metal that is necessary for all organisms but toxic when present in excess. Different mechanisms to avoid copper toxicity have been reported to date in pathogenic organisms such as Cryptococcus neoformans and Candida albicans . However, little if anything is known about pathogenic protozoans despite their importance in human and veterinary medicine. Naegleria fowleri is a free-living amoeba that occurs naturally in warm fresh water and can cause a rapid and deadly brain infection called primary amoebic meningoencephalitis (PAM). Here, we describe the mechanisms employed by N. fowleri to tolerate high copper concentrations, which include various strategies such as copper efflux mediated by a copper-translocating ATPase and upregulation of the expression of antioxidant enzymes and obscure hemerythrin-like and protoglobin-like proteins. The combination of different mechanisms efficiently protects the cell and ensures its high copper tolerance, which can be advantageous both in the natural environment and in the host. Nevertheless, we demonstrate that copper ionophores are potent antiamoebic agents; thus, copper metabolism may be considered a therapeutic target.

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“… 3 Some HLPs possess the same sequence motif as hemerythrin, while others have HHEHHE or HHEEHHE motifs. 4 In contrast to these motifs, the sequence motif in the mycobacterial HLPs proteins is HHEYHHE. 2 These are the only group of HLPs that utilize a Tyr as an iron ligand.…”

Section: Introductionmentioning

confidence: 99%

Correlation of Conservation of Sequence and Structures of Mycobacterial Hemerythrin-like Proteins with Evolutionary Relationship and Host Pathogenicity

Nogueira

Marchi-Salvador

et al. 2020

ACS Omega

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The Rv2633c gene of Mycobacterium tuberculosis , which plays a role in infection, encodes a hemerythrin-like protein (HLP). The crystal structure of an orthologue of Rv2633c, the HLP from Mycobacterium kansasii , revealed that it possessed structural features that were distinct from other hemerythrins and HLPs. These and other orthologous proteins comprise a distinct class of non-heme di-iron HLPs that are only found in mycobacteria. This study presents an analysis and comparison of protein sequences, putative structures, and evolutionary relationship of HLPs from 20 mycobacterial species that are known to cause tuberculosis or pulmonary disorders in humans. The results of this analysis allowed correlation of the physicochemical characteristics of amino acid residues that are substituted in these highly conserved sequences with their position in structures, possible effects on function, and evolutionary relationships. The sequences of the proteins from M. tuberculosis , Mycobacterium bovis, and other members of the M. tuberculosis complex, which cause tuberculosis, have substitutions not seen in the other non-tuberculous mycobacteria. Furthermore, groups of species that are closely related, based on phylogenetic analysis, possess substitutions of otherwise conserved residues not seen in other species that are less related. This information is correlated with the occurrence and clinical presentations of these groups of mycobacterial species. The results of this study provide a framework for structure–function studies to determine how subtle differences in the primary sequences of members of this family of proteins correlate with their structures and activities and how this may influence the infectious properties of the host species.

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Structure, function and evolution of the hemerythrin‐like domain superfamily

Cited by 39 publications

References 54 publications

Crystal structure of a hemerythrin-like protein from Mycobacterium kansasii and homology model of the orthologous Rv2633c protein of M. tuberculosis

Crystal structure of a hemerythrin-like protein from Mycobacterium kansasii and homology model of the orthologous Rv2633c protein of M. tuberculosis

Copper detoxification machinery of the brain-eating amoeba Naegleria fowleri involves copper-translocating ATPase and the antioxidant system

Correlation of Conservation of Sequence and Structures of Mycobacterial Hemerythrin-like Proteins with Evolutionary Relationship and Host Pathogenicity

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