Serine protease inhibitors and human wellbeing interplay: new insights for old friends

Abstract

Serine Protease Inhibitors (Serpins) control tightly regulated physiological processes and their dysfunction is associated to various diseases. Thus, increasing interest is given to these proteins as new therapeutic targets. Several studies provided functional and structural data about human serpins. By comparison, only little knowledge regarding bacterial serpins exists. Through the emergence of metagenomic studies, many bacterial serpins were identified from numerous ecological niches including the human gut microbiota. The origin, distribution and function of these proteins remain to be established. In this report, we shed light on the key role of human and bacterial serpins in health and disease. Moreover, we analyze their function, phylogeny and ecological distribution. This review highlights the potential use of bacterial serpins to set out new therapeutic approaches.

Keywords: Disease; Function; Homeostasis; Human gut microbiota; Serine protease inhibitors.

Figure 1. Serpin structure and mechanism of inhibition.

(A) The RCL (Blue) is recognized by a serine protease (green). After cleavage, RCL rapidly inserts into β-sheet and forms a covalent serpin-protease complex. (B) Close-up view of the interaction between the serpin and its target protease (adapted from Song et al., 2011, permission license number 4545950475192).

Figure 2. Bacterial serpins distribution.

Protein sequences and their taxonomic assignation were retrieved from public database NCBI. Taxonomic lineages are represented in different colors. Phylogenetic tree was built with PhyloT (https://phylot.biobyte.de/) and ITOL.

Figure 3. Distribution of bacterial serpin in ecological niches.

The pie-chart represents the relative percentage of serpins in various ecological niches.