Protist and Fungal Metaxin-like Proteins: Relationship to Vertebrate Metaxins that Function in Protein Import into Mitochondria

Adolph, Kenneth W

doi:10.1101/2021.01.05.425400

Cited by 3 publications

(5 citation statements)

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“…In addition, metaxin-like proteins are encoded in the genomes of bacteria such as Pseudomonas aeruginosa and Francisella tularensis, both causes of human disease (Adolph, 2020b). Furthermore, metaxin-like proteins are present in protists -eukaryotes that are neither animals, plants, nor fungi -and in fungi (Adolph, 2021(Adolph, , 2022. Examples of protists with genes for metaxin-like proteins are the model alga Chlamydomonas reinhardtii, the protozoan Amoeba proteus, and the parasite Trypanosoma vivax.…”

Section: Introductionmentioning

confidence: 99%

FAXC Proteins of Vertebrates and Invertebrates: Relationship to Metaxin Proteins

Adolph

2023

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FAXC proteins of vertebrates and invertebrates are shown to possess structural features similar to the metaxins, and can therefore be categorized as metaxin-like proteins. A variety of vertebrate and invertebrate species were found to encode FAXC (Failed Axon Connections) proteins. These are predicted proteins. Among the vertebrate species are human, mouse, zebrafish, and Xenopus. For invertebrates, FAXC proteins were most common in phyla that include Mollusca, Arthropoda, Cnidaria, and Placozoa. The presence of characteristic GST_N_Metaxin and GST_C_Metaxin protein domains was an important criterion in identifying the FAXCs as metaxin-like. In addition, the Tom37 domain was frequently found, especially in vertebrates. Also important was the possession of segments of alpha-helical secondary structure in a pattern of eight helices like that of metaxin 1 and other metaxins. Both the domain structures and alpha-helical structures are characteristic metaxin-like features. But alignment of protein sequences of both vertebrate and invertebrate FAXCs with metaxin proteins demonstrated that FAXCs and metaxins have low percentages of identical amino acids, about 20%. Therefore, FAXCs and metaxins are related, but are not the same protein. As revealed by phylogenetic analysis, vertebrate FAXCs and vertebrate metaxins 1, 2, and 3 constitute separate but related groups of proteins. Distinct phylogenetic groups were also observed for invertebrate FAXCs and invertebrate metaxins 1 and 2. The FAXC genes have neighboring genes that differ from the neighboring genes of metaxins. For vertebrates, the genes adjacent to FAXC genes are highly conserved. For invertebrates, the genes that neighbor FAXC genes are not the same as for vertebrates, but are conserved among different invertebrates. Invertebrates can have multiple FAXC genes, up to at least 12 or 13 genes. In some cases, the multiple FAXC genes exist as a cluster of genes in close proximity.

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Section: Introductionmentioning

confidence: 99%

FAXC Proteins of Vertebrates and Invertebrates: Relationship to Metaxin Proteins

Adolph

2023

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“…Alpha-helical regions, nine for plants and eight for bacteria, are the dominant feature. For protist metaxin-like proteins, the pattern of nine α-helices also resembles the pattern for human metaxin 1 (Adolph, 2021). The protists, eukaryotic organisms that are neither animals, plants, nor fungi, include animal-like protists such as Amoeba proteus (Amoebozoa) and plant-like protists such as the alga Chlorella variabilis (Chlorophyta).…”

Section: Secondary Structures Of the Multiple Metaxin-like Proteins Of Fungi: Alignments Of α-Helical Segmentsmentioning

confidence: 92%

“…A previous publication (Adolph, 2021) reported the existence of metaxin-like proteins in fungi representing major fungal taxonomic divisions, most commonly the Mucoromycota and Ascomycota divisions. For these fungi, a single metaxin-like protein was usually detected, with the GST_N_Metaxin, GST_C_Metaxin, and Tom37 domains that identify, along with other criteria, the protein as metaxin-like.…”

Section: Introductionmentioning

confidence: 99%

“…As examples, metaxin-like proteins are found in Francisella tularensis, a human pathogen, and Colwellia psychrerythraea, an obligate psychrophile (thrives in permanently cold temperatures). Protists and fungi likewise possess metaxin-like proteins (Adolph, 2021). Protists with these proteins include animal-like protists such as protozoa and amoebae, and plant-like protists such as phytoplankton and algae.…”

Section: Introductionmentioning

confidence: 99%

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The Metaxin Mitochondrial Import Proteins: Multiple Metaxin-like Proteins in Fungi

Adolph

2022

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Multiple metaxin-like proteins are shown to exist in fungi, as also found for the metaxin proteins of vertebrates and invertebrates. In vertebrates, metaxins 1 and 2 are mitochondrial membrane proteins that function in the import of proteins into mitochondria. Fungal metaxin-like proteins were identified by criteria including their homology with human metaxins and the presence of characteristic GST_N_Metaxin, GST_C_Metaxin, and Tom37 protein domains. Fungi in different taxonomic divisions (phyla) were found to possess multiple metaxin-like proteins. These include the Ascomycota, Basidiomycota, Blastocladiomycota, Chytridiomycota, Mucoromycota, Neocallimastigomycota, and Zoopagomycota divisions. Most fungi with multiple metaxin-like proteins contain two proteins, designated MTXa and MTXb. Amino acid sequence alignments show a high degree of homology among MTXa proteins, with over 60% amino acid identities, and also among MTXb proteins of fungi in the same division. But very little homology is observed in aligning MTXa with MTXb proteins of the same or different fungi. Both the MTXa proteins and MTXb proteins have the protein domains that characterize the metaxins and metaxin-like proteins: GST_N_Metaxin, GST_C_Metaxin, and Tom37. The metaxins and metaxin-like proteins of vertebrates, invertebrates, plants, protists, and bacteria all possess these domains. The secondary structures of MTXa and MTXb proteins are both dominated by similar patterns of α-helical segments, but extensive β-strand segments are absent. Nine highly conserved α-helical segments are present, the same as other metaxins and metaxin-like proteins. Phylogenetic analysis reveals that MTXa and MTXb proteins of fungi form two separate and distinct groups. These groups are also separate from the groups of vertebrate metaxins, metaxin-related Sam37 proteins of yeasts, and metaxin-like FAXC proteins.

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“…4 Three metaxins (1, 2, and 3) have been revealed in vertebrates including humans and also the mouse (genome sequence: Mouse Genome Sequencing Consortium, 2002), frog Xenopus laevis (Session et al, 2016), and zebrafish Danio rerio (Howe et al, 2013). Moreover, metaxinlike proteins have been detected in invertebrates (Adolph, 2020a), plants and bacteria (Adolph, 2020b), and protists and fungi (Adolph, 2021). FAXC (failed axon connections) proteins are also members of the family of metaxin-like proteins (Adolph, 2023).…”

Section: Introductionmentioning

confidence: 99%

CDR Proteins ofC.elegansand Related Species: Relationship to Metaxin and FAXC Proteins

Adolph

2024

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CDR (cadmium-responsive) proteins of the nematodeC. elegansand related species are shown to have structural homology to metaxin proteins and FAXC (failed axon connections) proteins of vertebrates and invertebrates. Unlike the metaxin and FAXC proteins, however, the predicted CDR proteins are only encoded in the genomes of nematodes, and not in vertebrates or other invertebrates. Metaxin-like structural features of CDR proteins are shown in this report to include: (1) GST_N_Metaxin and GST_C_Metaxin conserved protein domains, (2) metaxin-like patterns of α-helical secondary structure, and (3) a special 4-stranded β-sheet motif shared with the metaxins. FAXC proteins also possess these structural features. Phylogenetic analysis revealed that CDR proteins are related to metaxins 1, 2, and 3 and to FAXC proteins, although more closely to FAXC proteins. Nevertheless, all three types of proteins – CDR, FAXC, and metaxin – are related by evolution. Although CDR proteins have structural homology to metaxin and FAXC proteins, pairwise alignments of CDR proteins with metaxins and FAXCs demonstrated only low percentages of identical amino acids. CDR proteins can therefore be considered a separate category of proteins, distinct from metaxin and FAXC proteins. The CDR genes ofC. elegansconsist of a family of seven genes,cdr-1tocdr-7, which form a cluster of closely adjacent genes on chromosome V. Multiple genes were also found for the related speciesC. briggsaeandC. remanei. Alignment of pairs ofC. elegansCDR protein sequences encoded by differentcdrgenes demonstrated a high level of sequence homology. The neighboring genes of theC.elegans cdrgenes are different than the genes adjacent to theC.elegans faxcgenes and themtx-1andmtx-2metaxin genes.

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Protist and Fungal Metaxin-like Proteins: Relationship to Vertebrate Metaxins that Function in Protein Import into Mitochondria

Cited by 3 publications

References 33 publications

FAXC Proteins of Vertebrates and Invertebrates: Relationship to Metaxin Proteins

FAXC Proteins of Vertebrates and Invertebrates: Relationship to Metaxin Proteins

The Metaxin Mitochondrial Import Proteins: Multiple Metaxin-like Proteins in Fungi

CDR Proteins ofC.elegansand Related Species: Relationship to Metaxin and FAXC Proteins

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