Low reduction potential cytochrome b5 isotypes of Giardia intestinalis

Pazdzior, Robert; Yang, Zhen Alice; Mesbahuddin, Mirfath Sultana; Yee, Janet; Est, Art van der; Rafferty, Steven P.

doi:10.1016/j.exppara.2015.08.004

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…This protein belongs to a type II group of soluble b5 cytochromes, which were identified in a number of protists, including anaerobes, and for which no specific function, except for a general role in electron-transporting processes, has been proposed. 47 Cytochrome b5 orthologs from Giardia intestinalis have a conspicuously low reduction potential (À170 to À140 mV) 61 in comparison with type I mammalian microsomal homologs (0-10 mV). 62 The trichomonad cytochrome b5 was not characterized, but if it has a reduction potential similar to that of giardial orthologs, and its interaction with the cytosolic hydrogenase also occurred in vivo, then it could serve as a potent reductant transferring the reducing power of hydrogen to downstream redox reactions.…”

Section: Discussionmentioning

confidence: 99%

A cytosolic ferredoxin-independent hydrogenase possibly mediates hydrogen uptake in Trichomonas vaginalis

et al. 2022

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Section: Discussionmentioning

confidence: 99%

A cytosolic ferredoxin-independent hydrogenase possibly mediates hydrogen uptake in Trichomonas vaginalis

et al. 2022

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“…Many of them have also maintained a surface tryptophan residue analogous to Trp 114 of Ncb5or. The Giardia proteins were shown to exhibit redox potentials 54 similar to those determined for Ncb5or, 2 which are considerably more negative than for microsomal b 5 s. The Giardia proteins and Ncb5or also share EPR spectroscopic signatures that are characteristic of orthogonal His ligands 54 . It is reasonable to conclude that these proteins have evolved from the common N/b5 ancestor of Ncb5or, RLF, and IRC21, perhaps with divergent functions 53,54 .…”

Section: Resultsmentioning

confidence: 70%

“…The Giardia proteins were shown to exhibit redox potentials 54 similar to those determined for Ncb5or, 2 which are considerably more negative than for microsomal b 5 s. The Giardia proteins and Ncb5or also share EPR spectroscopic signatures that are characteristic of orthogonal His ligands 54 . It is reasonable to conclude that these proteins have evolved from the common N/b5 ancestor of Ncb5or, RLF, and IRC21, perhaps with divergent functions 53,54 . This notion is supported by the observation of cytochrome b 5 proteins in protists ( Trypanosoma and Dictyostelium ) that share the same b 5 core 53 and the N‐terminal motif as that in Ncb5or, including the Trp 114 and Trp 37 residues, respectively (Figure S5).…”

Section: Resultsmentioning

confidence: 99%

“…54 It is reasonable to conclude that these proteins have evolved from the common N/b5 ancestor of Ncb5or, RLF, and IRC21, perhaps with divergent functions. 53,54 This notion is supported by the observation of cytochrome b 5 proteins in protists (Trypanosoma and Dictyostelium) that share the same b 5 core 53 and the N-terminal motif as that in Ncb5or, including the Trp 114 and Trp 37 residues, respectively (Figure S5).…”

Section: The B 5 Cores Of Ncb5or and The Rice Rlf Protein Have Identi...mentioning

confidence: 99%

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The N‐terminal intrinsically disordered region of Ncb5or docks with the cytochrome b₅ core to form a helical motif that is of ancient origin

Benson,

Deng,

Kashipathy

et al. 2023

Proteins

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NADH cytochrome b5 oxidoreductase (Ncb5or) is a cytosolic ferric reductase implicated in diabetes and neurological conditions. Ncb5or comprises cytochrome b5 (b5) and cytochrome b5 reductase (b5R) domains separated by a CHORD‐Sgt1 (CS) linker domain. Ncb5or redox activity depends on proper inter‐domain interactions to mediate electron transfer from NADH or NADPH via FAD to heme. While full‐length human Ncb5or has proven resistant to crystallization, we have succeeded in obtaining high‐resolution atomic structures of the b5 domain and a construct containing the CS and b5R domains (CS/b5R). Ncb5or also contains an N‐terminal intrinsically disordered region of 50 residues that has no homologs in other protein families in animals but features a distinctive, conserved L34MDWIRL40 motif also present in reduced lateral root formation (RLF) protein in rice and increased recombination center 21 in baker's yeast, all attaching to a b5 domain. After unsuccessful attempts at crystallizing a human Ncb5or construct comprising the N‐terminal region naturally fused to the b5 domain, we were able to obtain a high‐resolution atomic structure of a recombinant rice RLF construct corresponding to residues 25–129 of human Ncb5or (52% sequence identity; 74% similarity). The structure reveals Trp120 (corresponding to invariant Trp37 in Ncb5or) to be part of an 11‐residue α‐helix (S116QMDWLKLTRT126) packing against two of the four helices in the b5 domain that surround heme (α2 and α5). The Trp120 side chain forms a network of interactions with the side chains of four highly conserved residues corresponding to Tyr85 and Tyr88 (α2), Cys124 (α5), and Leu47 in Ncb5or. Circular dichroism measurements of human Ncb5or fragments further support a key role of Trp37 in nucleating the formation of the N‐terminal helix, whose location in the N/b5 module suggests a role in regulating the function of this multi‐domain redox enzyme. This study revealed for the first time an ancient origin of a helical motif in the N/b5 module as reflected by its existence in a class of cytochrome b5 proteins from three kingdoms among eukaryotes.

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“…Both cases represent absolute novelties as cyp is conserved across almost the entire tree of life (Nelson, 2018). The loss of cyp was previously only reported from protozoan parasites, such as Plasmodium falciparum (Welch, 1897) (Wisedpanichkij et al, 2011), Giardia intestinalis (Lambl, 1859) (Pazdzior et al, 2015), and Encephalitozoon cuniculi Levaditi, Nicolau & Schoen, 1923(Shaheen et al, 2020. In other flatworms, e.g.…”

Section: Potential Gene Expansions Contractions and Losses In Monogen...mentioning

confidence: 96%

Copy numbers of stress response genes reflect difference in adaptive potential of metazoan parasites

Cruz-Laufer,

Vanhove,

Geraerts

et al. 2024

Preprint

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Stress responses are key for parasite survival and, thus, also the evolutionary success of these organisms. However, the evolution of the molecular pathways dealing with environmental stressors are poorly understood as most research focuses either on few selected human-relevant pathogens or major parasite clades. Here, we comparatively investigate, for the first time, antioxidant, heat shock, and behaviour-related genes in the two parasite lineages Cichlidogyrus and Kapentagyrus from the same family Dactylogyridae through whole-genome sequencing data of 11 species. The two lineages differ concerning their species and ecological diversity, which is expected to affect the diversity of their stress responses and, hence, their adaptive potential. Through an exon bait capture approach, we assembled the putative protein sequences of 43 stress-related genes. We discovered that Cichlidogyrus presented higher copy numbers of stress genes (70 kDA heat shock protein, glutathione S-transferase genes) than Kapentagyrus. This difference might explain the ability of species of Cichlidogyrus to colonise various cichlid and non-cichlid lineages. In comparison to most other organisms studied so far, we also observed a previously unreported absence of cytochrome P450 and sigma class glutathione S-transferase in monogenean flatworms. This pattern aligns with previously published genome annotations of monogeneans.

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Low reduction potential cytochrome b5 isotypes of Giardia intestinalis

Cited by 7 publications

References 29 publications

A cytosolic ferredoxin-independent hydrogenase possibly mediates hydrogen uptake in Trichomonas vaginalis

A cytosolic ferredoxin-independent hydrogenase possibly mediates hydrogen uptake in Trichomonas vaginalis

The N‐terminal intrinsically disordered region of Ncb5or docks with the cytochrome b₅ core to form a helical motif that is of ancient origin

Copy numbers of stress response genes reflect difference in adaptive potential of metazoan parasites

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Low reduction potential cytochrome b5 isotypes of Giardia intestinalis

Cited by 7 publications

References 29 publications

A cytosolic ferredoxin-independent hydrogenase possibly mediates hydrogen uptake in Trichomonas vaginalis

A cytosolic ferredoxin-independent hydrogenase possibly mediates hydrogen uptake in Trichomonas vaginalis

The N‐terminal intrinsically disordered region of Ncb5or docks with the cytochrome b5 core to form a helical motif that is of ancient origin

Copy numbers of stress response genes reflect difference in adaptive potential of metazoan parasites

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The N‐terminal intrinsically disordered region of Ncb5or docks with the cytochrome b₅ core to form a helical motif that is of ancient origin