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| Main Authors: | , , , , |
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| Format: | Artículo científico |
| Language: | en |
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International journal of molecular sciences
2024
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39408954/ |
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| _version_ | 1868266292617674752 |
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| author | Wang, Qingyue Yuan, Zihao Xu, Hang Chen, Yuan Sun, Li |
| author_facet | Wang, Qingyue Yuan, Zihao Xu, Hang Chen, Yuan Sun, Li Wang, Qingyue Yuan, Zihao Xu, Hang Chen, Yuan Sun, Li |
| collection | PubMed - marine biology |
| contents | The Evolution and Biological Activity of Metazoan Mixed Lineage Kinase Domain-Like Protein (MLKL). Wang, Qingyue Yuan, Zihao Xu, Hang Chen, Yuan Sun, Li Animals Protein Kinases Humans Phylogeny Evolution, Molecular Necroptosis Protein Domains Amino Acid Sequence Invertebrates In mammals, mixed lineage kinase domain-like protein (MLKL) is the executor of necroptosis. MLKL comprises an N-terminal domain (NTD), which alone suffices to trigger necroptosis by forming pores in the plasma membrane, and a C-terminal domain that inhibits the NTD activity. Evolutionarily, MLKL is poorly conserved in animals and not found in Protostomia. Although MLKL orthologs exist in invertebrate Deuterostomia, the biological activity of invertebrate MLKL is unknown. Herein, we examined 34 metazoan phyla and detected MLKL not only in Deuterostomia but also in Protostomia (Rotifera). The Rotifera MLKL exhibited low identities with non-Rotifera MLKL but shared relatively high identities with non-metazoan MLKL. In invertebrates, MLKL formed two phylogenetic clades, one of which was represented by Rotifera. In vertebrates, MLKL expression was tissue-specific and generally rich in immune organs. When expressed in human cells, the MLKL-NTD of Rotifera, Echinodermata, Urochordata, and Cephalochordata induced strong necroptosis. The necroptotic activity of Rotifera MLKL depended on a number of conserved residues. Together these findings provided new insights into the evolution of MLKL in Metazoa and revealed the biological activity of invertebrate MLKL. |
| format | Artículo científico |
| id | pubmed_39408954 |
| institution | PubMed |
| language | en |
| publishDate | 2024 |
| publisher | International journal of molecular sciences |
| record_format | pubmed |
| spellingShingle | The Evolution and Biological Activity of Metazoan Mixed Lineage Kinase Domain-Like Protein (MLKL). Wang, Qingyue Yuan, Zihao Xu, Hang Chen, Yuan Sun, Li Animals Protein Kinases Humans Phylogeny Evolution, Molecular Necroptosis Protein Domains Amino Acid Sequence Invertebrates The Evolution and Biological Activity of Metazoan Mixed Lineage Kinase Domain-Like Protein (MLKL). Wang, Qingyue Yuan, Zihao Xu, Hang Chen, Yuan Sun, Li Animals Protein Kinases Humans Phylogeny Evolution, Molecular Necroptosis Protein Domains Amino Acid Sequence Invertebrates In mammals, mixed lineage kinase domain-like protein (MLKL) is the executor of necroptosis. MLKL comprises an N-terminal domain (NTD), which alone suffices to trigger necroptosis by forming pores in the plasma membrane, and a C-terminal domain that inhibits the NTD activity. Evolutionarily, MLKL is poorly conserved in animals and not found in Protostomia. Although MLKL orthologs exist in invertebrate Deuterostomia, the biological activity of invertebrate MLKL is unknown. Herein, we examined 34 metazoan phyla and detected MLKL not only in Deuterostomia but also in Protostomia (Rotifera). The Rotifera MLKL exhibited low identities with non-Rotifera MLKL but shared relatively high identities with non-metazoan MLKL. In invertebrates, MLKL formed two phylogenetic clades, one of which was represented by Rotifera. In vertebrates, MLKL expression was tissue-specific and generally rich in immune organs. When expressed in human cells, the MLKL-NTD of Rotifera, Echinodermata, Urochordata, and Cephalochordata induced strong necroptosis. The necroptotic activity of Rotifera MLKL depended on a number of conserved residues. Together these findings provided new insights into the evolution of MLKL in Metazoa and revealed the biological activity of invertebrate MLKL. |
| title | The Evolution and Biological Activity of Metazoan Mixed Lineage Kinase Domain-Like Protein (MLKL). |
| topic | Animals Protein Kinases Humans Phylogeny Evolution, Molecular Necroptosis Protein Domains Amino Acid Sequence Invertebrates |
| url | https://pubmed.ncbi.nlm.nih.gov/39408954/ |