Invertebrate Metaxins 1 and 2: Widely Distributed Proteins Homologous to Vertebrate Metaxins Implicated in Protein Import into Mitochondria

2021

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Metaxin-like proteins are shown to be encoded in the genomes of a wide range of protists and fungi. The metaxin proteins were originally described in humans and mice, and were experimentally demonstrated to have a role in the import of nascent proteins into mitochondria. In this study, metaxin-like proteins of protists and fungi predicted from genome sequences were identified by criteria including their sequence homology with vertebrate metaxin proteins and the existence of distinctive metaxin protein domains. Protists of diverse taxa, including amoebae, protozoa, phytoplankton, downy mildews, water molds, and algae, were found to possess genes for metaxin-like proteins. With fungi, the important taxonomic divisions (phyla) of Ascomycota, Basidiomycota, Chytridiomycota, Mucoromycota, and Zoopagomycota had species with metaxin-like protein genes. The presence of distinctive GST_N_Metaxin, GST_C_Metaxin, and Tom37 domains in the predicted proteins indicates that the protist and fungal proteins are related to the vertebrate metaxins. However, the metaxin-like proteins are not direct homologs of vertebrate metaxins 1, 2, or 3, but have similarity to each of the three. The alignment of the metaxin-like proteins of a variety of protists with vertebrate metaxins 1 and 2 showed about 26% and 19% amino acid identities, respectively, while for fungal metaxin-like proteins, the identities were about 29% and 23%. The different percentages with the two vertebrate metaxins indicates that the metaxin-like proteins are both metaxin 1-like and, to a lesser degree, metaxin 2-like. The secondary structures of protist and fungal metaxin-like proteins both consist of nine α-helical segments, the same as for the vertebrate metaxins, with a negligible contribution from β-strand. Phylogenetic analysis demonstrated that the protist and fungal metaxin-like proteins and the vertebrate metaxins form distinct and separate groups, but that the groups are derived from a common ancestral protein sequence.

Section: Conserved Protein Domains Of Protist and Fungal Metaxin-likementioning

confidence: 63%

Section: Alpha-helical Secondary Structures Of Protist and Fungal Metmentioning

confidence: 86%

Section: Presence Of Metaxin-like Proteins In Protists and Fungimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2021

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“…Furthermore, metaxin proteins were detected among invertebrates such as the nematode C. elegans and the fruit fly Drosophila melanogaster. A broad range of invertebrate phyla were found to possess proteins homologous to vertebrate metaxins 1 and 2 (Adolph, 2020). The aim of the study reported here was to investigate whether proteins homologous to the metaxins also exist in plants and bacteria.…”

Section: Introductionmentioning

confidence: 99%

Plant and Bacterial Metaxin-like Proteins: Novel Proteins Related to Vertebrate Metaxins Involved in Uptake of Nascent Proteins into Mitochondria

2020

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The metaxins were originally identified as vertebrate proteins of the outer mitochondrial membrane involved in protein import into mitochondria. Metaxin proteins have also been found in diverse invertebrate phyla. The present study is concerned with examining whether metaxinlike proteins occur in plants and bacteria. Metaxin-like proteins were revealed by their homology with human metaxins and the possession of characteristic GST_Metaxin protein domains. The results demonstrate that metaxin-like proteins exist in plants that include a wide variety of angiosperms, both eudicots and monocots, and other plant groups. Metaxin-like proteins can also be detected in bacteria, particularly in the Proteobacteria phylum, but also in different bacterial phyla. Phylogenetic analysis indicates that plant metaxin-like proteins, bacterial metaxin-like proteins, and vertebrate metaxins form distinct phylogenetic groups, but are related. Metaxin-like proteins, however, are only distantly related to GSTs (glutathione S-transferase proteins). A similar degree of homology is found in aligning the amino acid sequences of plant and bacterial metaxin-like proteins with human metaxins 1, 2, and 3 and other vertebrate metaxins. The amino acid identities range from about 22%-28% for each alignment. The presence of two conserved protein domains, GST_N_Metaxin and GST_C_Metaxin, in both plant and bacterial metaxin-like proteins provides evidence that these proteins are related to the vertebrate and invertebrate metaxins. The metaxin-like proteins have predicted secondary structures that are dominated by alpha-helical segments, like the vertebrate and invertebrate metaxins. 7 3. RESULTS AND DISCUSSION 3.1. Existence of Metaxin-like Proteins in Plants and Bacteria Among plants, metaxin-like proteins are found in a wide variety of angiosperms, both eudicots and monocots. The proteins, largely predicted from genomic sequences, were identified by their homology with vertebrate metaxins and the presence of characteristic GST_Metaxin protein domains. Metaxin-like proteins in eudicots are the most common. Examples of eudicots with metaxin-like proteins include the model flowering plant Arabidopsis, the potato, morning glory, and pumpkin. Among the monocots are wheat, the model grass Brachypodium distachyon, asparagus, and barley. Eudicots with metaxin-like proteins include both asterids and rosids. Examples of these asterids are Genlisea aurea, a carnivorous plant with the smallest known angiosperm genome, the tea plant, a wild tomato species, and a chili pepper. Rosids with metaxin-like proteins include the China rose, turnip, pink shepherd's purse (a close relative of Arabidopsis), and the pomegranate. Other types of plants with metaxin-like proteins that are model plants in biology research are the moss Physcomitrella patens and the liverwort Marchantia polymorpha. The bacterial species that have metaxin-like proteins are primarily in the Proteobacteria phylum. Gammaproteobacteria and Alphaproteobacteria are the most common taxonomic classes wit...

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

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.