TAILS N-terminomics of human platelets reveals pervasive metalloproteinase-dependent proteolytic processing in storage.

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We used a dedicated N-terminomics technique, iTRAQ terminal amine isotopic labeling of substrates (TAILS), to characterize the human platelet N-terminome, proteome, and posttranslational modifications throughout platelet storage over 9 days under blood-banking conditions. From the identified 2938 proteins and 7503 unique peptides, we characterized N-terminal methionine excision, co- and posttranslational Nα acetylation, protein maturation, and proteolytic processing of proteins in human platelets. We also identified for the first time 10 proteins previously classified by the Human Proteome Organization as \"missing\" in the human proteome. Most N termini (77%) were internal neo-N termini (105 were novel potential alternative translation start sites, and 2180 represented stable proteolytic products), thus highlighting a prominent yet previously uncharacterized role of proteolytic processing during platelet storage. Protease inhibitor studies revealed metalloproteinases as being primarily responsible for proteolytic processing (as opposed to degradation) during storage. System-wide identification of metalloproteinase and other proteinase substrates and their respective cleavage sites suggests novel mechanisms of the effect of proteases on protein activity and platelet function during storage. All data sets and metadata are available through ProteomeXchange with the data set identifier PXD000906.", "claims": [{"id": "claim-target-result", "statement": "The paper used TAILS (iTRAQ terminal amine isotopic labeling of substrates) proteomics, and all datasets and metadata are available through ProteomeXchange under identifier PXD000906; no statistical method is stated in the provided text.", "kind": "quantitative", "target": {"value": 77.0, "unit": "per cent", "tolerance": null, "source": "Most N termini (77%) were internal neo-N termini (105 were novel potential alternative translation start sites, and 2180 represented stable proteolytic products), thus highlighting a prominent yet previously uncharacterized role of proteolytic processing during platelet storage."}, "evidence": [{"asset": "source:pmid:25331112", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "We used a dedicated N-terminomics technique, iTRAQ terminal amine isotopic labeling of substrates (TAILS), to characterize the human platelet N-terminome, proteome, and posttranslational modifications throughout platelet storage over 9 days under blood-banking conditions."}, {"asset": "source:pmid:25331112", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Most N termini (77%) were internal neo-N termini (105 were novel potential alternative translation start sites, and 2180 represented stable proteolytic products), thus highlighting a prominent yet previously uncharacterized role of proteolytic processing during platelet storage."}, {"asset": "source:pmid:25331112", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "All data sets and metadata are available through ProteomeXchange with the data set identifier PXD000906."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper used TAILS (iTRAQ terminal amine isotopic labeling of substrates) proteomics, and all datasets and metadata are available through ProteomeXchange under identifier PXD000906; no statistical method is stated in the provided text.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:25331112"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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