Early eukaryotic origins and metazoan elaboration of MAPR family proteins

Mol Phylogenet Evol. 2020 Jul;148:106814. doi: 10.1016/j.ympev.2020.106814. Epub 2020 Apr 8.

Abstract

The 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 genes (PGRMC-like, Neuferricin and Neudesin). Here we show that all three animal MAPR genes were already present in the common ancestor of the opisthokonts (comprising animals and fungi as well as related single-celled taxa). All three MAPR genes acquired extensions C-terminal to the cytb5 domain, 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 cnidarians and bilaterians, along with an early embryological organizer and synapsed neurons, and is strongly conserved in all bilaterian 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 animals (Metazoa). This study provides a conceptual framework for future studies, against which especially PGRMC1's multiple functions can perhaps be stratified and functionally dissected.

Keywords: Holozoa; Membrane-associated progesterone receptor; Multicellularity; Opisthokont; Organizer; Phylogeny; Protein evolution; Tyrosine phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Eukaryota / metabolism*
  • Evolution, Molecular
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Phylogeny
  • Protein Binding
  • Protein Domains
  • Receptors, Progesterone / chemistry
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism*

Substances

  • Membrane Proteins
  • Receptors, Progesterone