{"doi":"10.3390/proteomes11010008","title":"Non-Specific Signal Peptidase Processing of Extracellular Proteins in Staphylococcus aureus N315","abstract":"Staphylococcus aureus is one of the major community-acquired human pathogens, with growing multidrug-resistance, leading to a major threat of more prevalent infections to humans. A variety of virulence factors and toxic proteins are secreted during infection via the general secretory (Sec) pathway, which requires an N-terminal signal peptide to be cleaved from the N-terminus of the protein. This N-terminal signal peptide is recognized and processed by a type I signal peptidase (SPase). SPase-mediated signal peptide processing is the crucial step in the pathogenicity of S. aureus. In the present study, the SPase-mediated N-terminal protein processing and their cleavage specificity were evaluated using a combination of N-terminal amidination bottom-up and top-down proteomics-based mass spectrometry approaches. Secretory proteins were found to be cleaved by SPase, specifically and non-specifically, on both sides of the normal SPase cleavage site. The non-specific cleavages occur at the relatively smaller residues that are present next to the −1, +1, and +2 locations from the original SPase cleavage site to a lesser extent. Additional random cleavages at the middle and near the C-terminus of some protein sequences were also observed. This additional processing could be a part of some stress conditions and unknown signal peptidase mechanisms.","journal":"Proteomes","year":2023,"id":376515,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1139748,"name":"Sheetal D. Ovhal","orcid":"0000-0002-9199-4332","position":1,"is_corresponding":false},{"id":422869,"name":"Sujun Li","orcid":"0000-0001-5233-2005","position":2,"is_corresponding":false},{"id":379049,"name":"Jonathan A. Karty","orcid":"0000-0003-1022-9100","position":3,"is_corresponding":false},{"id":374937,"name":"Haixu Tang","orcid":"0000-0001-8963-8155","position":4,"is_corresponding":false},{"id":17057,"name":"PREDRAG RADIVOJAC","orcid":"0000-0002-6769-0793","position":5,"is_corresponding":false},{"id":788877,"name":"James P. Reilly","orcid":"0000-0002-9784-1804","position":6,"is_corresponding":false},{"id":240295,"name":"Santosh A. Misal","orcid":"0000-0002-8835-0130","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:16:32.368674Z","pmid":"36810564","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}