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Here we present the first systems-wide analysis of endoproteolysis in the genome-reduced pathogen <jats:italic>Mycoplasma hyopneumoniae<\/jats:italic>. 669 N-terminal peptides from 164 proteins were identified, demonstrating that functionally diverse proteins are processed, more than half of which 75 (53%) were accessible on the cell surface. Multiple cleavage sites were characterised, but cleavage with arginine in P1 predominated. Putative functions for a subset of cleaved fragments were assigned by affinity chromatography using heparin, actin, plasminogen and fibronectin as bait. Binding affinity was correlated with the number of cleavages in a protein, indicating that novel binding motifs are exposed, and protein disorder increases, after a cleavage event. Glyceraldehyde 3-phosphate dehydrogenase was used as a model protein to demonstrate this. We define the rules governing methionine excision, show that several aminopeptidases are involved, and propose that through processing, genome-reduced organisms can expand protein function.<\/jats:p>","DOI":"10.1038\/s41598-017-11296-9","type":"journal-article","created":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T07:29:08Z","timestamp":1504596548000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["N-terminomics identifies widespread endoproteolysis and novel methionine excision in a genome-reduced bacterial pathogen"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0322-2595","authenticated-orcid":false,"given":"Iain J.","family":"Berry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica M.","family":"Jarocki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Tacchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin B. A.","family":"Raymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Widjaja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Padula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P.","family":"Djordjevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,11]]},"reference":[{"key":"11296_CR1","doi-asserted-by":"publisher","first-page":"2637","DOI":"10.1002\/pmic.201400157","volume":"14","author":"EM Hartmann","year":"2014","unstructured":"Hartmann, E. M. & Armengaud, J. N-terminomics and proteogenomics, getting off to a good start. 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