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A Comprehensive Phylogenetic Analysis of the Serpin Superfamily

Overview
Journal Mol Biol Evol
Specialty Biology
Date 2021 Mar 21
PMID 33744972
Citations 27
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Abstract

Serine protease inhibitors (serpins) are found in all kingdoms of life and play essential roles in multiple physiological processes. Owing to the diversity of the superfamily, phylogenetic analysis is challenging and prokaryotic serpins have been speculated to have been acquired from Metazoa through horizontal gene transfer due to their unexpectedly high homology. Here, we have leveraged a structural alignment of diverse serpins to generate a comprehensive 6,000-sequence phylogeny that encompasses serpins from all kingdoms of life. We show that in addition to a central "hub" of highly conserved serpins, there has been extensive diversification of the superfamily into many novel functional clades. Our analysis indicates that the hub proteins are ancient and are similar because of convergent evolution, rather than the alternative hypothesis of horizontal gene transfer. This work clarifies longstanding questions in the evolution of serpins and provides new directions for research in the field of serpin biology.

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References
1.
Sochaj-Gregorczyk A, Ksiazek M, Waligorska I, Straczek A, Benedyk M, Mizgalska D . Plasmin inhibition by bacterial serpin: Implications in gum disease. FASEB J. 2020; 34(1):619-630. PMC: 8882047. DOI: 10.1096/fj.201901490RR. View

2.
Heit C, Jackson B, McAndrews M, Wright M, Thompson D, Silverman G . Update of the human and mouse SERPIN gene superfamily. Hum Genomics. 2013; 7:22. PMC: 3880077. DOI: 10.1186/1479-7364-7-22. View

3.
Ghendler Y, Arnon R, Fishelson Z . Schistosoma mansoni: isolation and characterization of Smpi56, a novel serine protease inhibitor. Exp Parasitol. 1994; 78(2):121-31. DOI: 10.1006/expr.1994.1013. View

4.
Cabrita L, Irving J, Pearce M, Whisstock J, Bottomley S . Aeropin from the extremophile Pyrobaculum aerophilum bypasses the serpin misfolding trap. J Biol Chem. 2007; 282(37):26802-26809. DOI: 10.1074/jbc.M705020200. View

5.
Kazemi S, Sabatier J . Venoms of Iranian Scorpions (Arachnida, Scorpiones) and Their Potential for Drug Discovery. Molecules. 2019; 24(14). PMC: 6680535. DOI: 10.3390/molecules24142670. View