COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein

摘要

Comparison of select hepcidin and coronavirus spike protein sequences. a A multiple sequence alignment of the C-terminal region of a number of coronavirus spike proteins (encompassing portions of the putative transmembrane and cytoplasmic tail segments), four hepcidins and the SARS-CoV-2 envelope protein is presented. The envelope sequence is provided only to demonstrate the cysteine residues with which the spike protein is proposed to form disulfide bridges [135]. The residue numbers are shown on the sides of each protein segment, and for proteins whose C-terminal sequences continue beyond the alignment, the full residue length is provided to the right. As per a color scheme used previously [111], dark green, grey and black highlights depict conserved, similar and identical residues, respectively. ‘Tr’ stands for Takifugu rubripes (Japanese pufferfish), ‘Rf’ for Rhinolophus ferrumequinum (greater horseshoe bat) and ‘Hs’ for Homo sapiens (human). The protein accession numbers of the sequences shown are, in order: (1) {"type":"entrez-protein","attrs":{"text":"AWH65954.1","term_id":"1386872252","term_text":"AWH65954.1"}}AWH65954.1, (2) {"type":"entrez-protein","attrs":{"text":"YP_009724390.1","term_id":"1796318598","term_text":"YP_009724390.1"}}YP_009724390.1, (3) {"type":"entrez-protein","attrs":{"text":"ANA96027.1","term_id":"1023043585","term_text":"ANA96027.1"}}ANA96027.1, (4) {"type":"entrez-protein","attrs":{"text":"XP_003965681.1","term_id":"410904403","term_text":"XP_003965681.1"}}XP_003965681.1, (5) {"type":"entrez-protein","attrs":{"text":"XP_029694670.1","term_id":"1698338386","term_text":"XP_029694670.1"}}XP_029694670.1, (6) ENSRFET00010014064.1, (7) {"type":"entrez-protein","attrs":{"text":"NP_066998.1","term_id":"10863973","term_text":"NP_066998.1"}}NP_066998.1 and (8) {"type":"entrez-protein","attrs":{"text":"QHD43418.1","term_id":"1791269092","term_text":"QHD43418.1"}}QHD43418.1. The domain illustration of the spike protein is based on ref. [132]. b A solved NMR structure of human hepcidin [65] (PDB: 2KEF), adopting an antiparallel beta-sheet fold, is visualized with its putative four disulfide bonds formed between eight cysteine residues. c The position of the disulfide bonds in the sequence of the mature human hepcidin is illustrated along with the potential palmitoylation residues (ten cysteines) of the cytoplasmic tail of the SARS-CoV-2 spike protein. The palmitate visual is as per ref. [77] with permission from the publisher (Springer Nature)