D3190: Electron transport across membranes: A phylogenetic analysis of insect cytochrome b561 proteins

Cytochrome b561s are a family of integral membrane proteins that transfer an electron across a membrane. Most eukaryotic species possess multiple cytb561 homologs, including eight in Drosophila melanogaster. While some insect cytochrome b561 proteins have been proposed to function as ferric reductases in the context of iron uptake, there has not been a systematic investigation of this protein family in insects. Through phylogenetic analyses of insect cytochrome b561s, we wish to better understand the commonalities and differences among these proteins, and how these factors might relate to putative biological function, with a specific focus on possible physiological roles in ferric reduction and iron metabolism. We performed a phylogenetic analysis of cytochrome b561 family members across nine insect species, representing eight insect orders, and identified four clades of cytochrome b561 members. The CG8399-like group had representatives in all insect species investigated and contains a mosquito-specific expansion. Two related clades, CG1275-like and nemy-like, are distinguished by cysteine-rich cytosolic loops in nemy-like sequences. We identified a novel long nemy-like sequence in Acyrthosiphum pisum that appears only to be present in aphids. The fourth clade includes insect species-related clusters and a group of proteins with a KXXXXKXH motif similar to a human CYB561D2/Tscytb. Cytochrome b561s are versatile proteins that potentially play a role in iron reduction and ascorbate regeneration, including in the context of peptide amidation, and may have roles related to membrane potential and reproduction. The expansions in different insect species suggest evolution of these proteins support specialized activities in related insect species.