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Early eukaryotic origins and metazoan elaboration of MAPR family proteins
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- BackgroundThe membrane-associated progesterone receptor (MAPR) family consists of heme-binding proteins containing a cytochrome b5(cytb5) domain characterized by the presence of a MAPR-specific interhelical insert region (MIHIR) between helices 3 and 4 of the canonical cytb5-domain fold. Animals possess three MAPR families (PGRMC-like, Neuferricin and Neudesin).ResultsHere we show that all animal MAPR families were already present in the common ancestor of the Opisthokonta (comprising animals and fungi as well as related protistan taxa). All three MAPR genes acquired extensions C-terminal to the cytb5domain, either before or with the evolution of animals. The archetypical MAPR protein, progesterone receptor membrane component 1 (PGRMC1), contains phosphorylated tyrosines Y139 and Y180. The combination of Y139/Y180 appeared in the common ancestor of Cnidaria and bilaterally symmetrical animals, along with an early embryological organizer and synapsed neurons, and is strongly conserved in all bilateral animals. A predicted protein interaction motif in the PGRMC1 MIHIR is potentially regulated by Y139 phosphorylation. A multilayered model of animal MAPR function acquisition includes some pre-metazoan functions (e.g., heme binding and cytochrome P450 interactions) and some acquired animal-specific functions that involve regulation of strongly conserved protein interaction motifs acquired by early-branching animals.ConclusionsThis study provides a conceptual framework for future studies, against which PGRMC1’s multiple functions can perhaps be stratified and functionally dissected. In accompanying papers we show that mutational perturbation of PGRMC1 phosphorylation status of the Y180 motif is associated with dramatic changes cell pasticity assayed by protein abundances, cell morphology, mitochondrial function, genomic stability, and epigenetic status, with pathways analysis associating Y180 mutation with processes related to organizer function. These combined works reveal previously unrecognized involvement of PGRMC1 in foundational animal processes of great relevance to disease.
- Subjects :
- 0106 biological sciences
0301 basic medicine
Opisthokont
Heme binding
Cell morphology
010603 evolutionary biology
01 natural sciences
Evolution, Molecular
03 medical and health sciences
0302 clinical medicine
Protein Domains
Phylogenetics
Cytochrome b5
Genetics
Animals
Amino Acid Sequence
Epigenetics
Molecular Biology
PGRMC1
Gene
Phylogeny
Ecology, Evolution, Behavior and Systematics
030304 developmental biology
0303 health sciences
biology
Eukaryota
Membrane Proteins
Cytochrome P450
biology.organism_classification
030104 developmental biology
Evolutionary biology
Holozoa
biology.protein
Phosphorylation
Receptors, Progesterone
030217 neurology & neurosurgery
Function (biology)
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....4cc023a9b67fef920aeca55ee60875e7
- Full Text :
- https://doi.org/10.1016/j.ympev.2020.106814