Reviewing Mechanistic Peptidomics in Body Fluids Focusing on Proteases

Abstract

The comprehension of how protease networks sculpt proteomes might help to disclose the functional annotation of the peptidome in health and disease. Envisioning to add new insights on the protease networks involved in the regulation of body fluid peptidomes, the authors apply Proteasix software to predict the proteases involved in the generation of the naturally occurring peptides present in six of the most studied human body fluids. Peptidome data is collected from the databases and from experimental studies. The analysis highlights 132 putative proteases from four families with the predominance of serine proteases and metalloproteases. From these, 49 proteases seem to be common to all fluids and are mostly associated to extracellular matrix organization as well as protein/peptide hormone processing. Data analysis also emphasizes: i) the similarity between plasma and CSF protease profiles; ii) that saliva and tears share proteases involved in the generation of peptides with antimicrobial activity; iii) that urine is the body fluid with the highest number of unique putative proteases, precluding an easy tracing of proteolytic events in this case. Taken together, the analysis emphasizes the intricate modus operandi of proteases, challenged by the interconnected pathways and amplification cascades in which they are involved.

Salicylic acid influences the protease activity and posttranslation modifications of the secreted peptides in the moss Physcomitrella patens

“…These facts can explain the large number of peptides without predicted sites of proteolysis in our study. Our results are in concordance with recent studies on mammals, which suggest that proteases make a great contribution to the proteome and peptidome formation of tissues and body fluids . For example, in humans, the most abundant classes of proteases involved in the peptidome shaping of body fluids are serine‐type proteases and metalloproteases.…”

“…Recent studies have shown that certain types of proteases can be involved in the generation of native peptides in human body fluids . However, which proteases are responsible for shaping the extracellular plant peptidome remains to be elucidated.…”

Peptidome: Chaos or Inevitability

“…The release of peptide hormones during the protease-specific cleavage of corresponding protein precursors at a specific site is well-studied in many organisms [ 67 , 68 ]. The architecture of these, mainly unfunctional, protein precursors is quite similar among plants, mammals, bacteria and yeast.…”

“…However, the role of proteases in shaping the whole intra- and extracellular peptidomes still remains poorly studied. Presumably, proteases make a significant contribution to the shaping of the secreted peptidome [ 16 , 68 ]. It was observed that treatment with stress phytohormones triggered the increase in activity of subtilisin-like serine protease, such as P69B, and papain-like cysteine proteases, such as PIP1 and some others in plants [ 83 , 88 ].…”

“…Analysis of the N- and C- ends of peptides in the plant secretome under stress conditions also showed the predominance of serine- and metalloproteases [ 16 ]. Serine, metalloprotease and cysteine protease activity have also been shown in secreted peptidomes of human bodily fluids [ 12 , 68 ].…”