{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Xml":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD065047/mqpar.xml"],"Raw":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD065047/L20222001846a.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD065047/L20222001845a.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD065047/L20222001843a.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD065047/L20222001848a.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD065047/L20222001844a.raw","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD065047/L20222001847a.raw"],"Fasta":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD065047/MOUSE.fasta"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD065047/txt.zip"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["roman.gonzalez@cabimer.es"],"submitter":["Román González-Prieto"],"technology_type":["Affinity purification coupled with mass spectrometry proteomics","Mass Spectrometry"],"software":["Not available"],"submitter_keywords":["Betaglycan/ heminth polygyrus/ signal transduction/ transforming growth factor-b/ low density protein"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD065047"],"sample_protocol":["Ten µg of TGM6 incubated with EZ-Link™ Sulfo-NHS-LC-Biotin (Pierce, 21335) for 30 minutes at RT°, the reaction was stopped by addition of 50 mM Tris-HCl pH 7.4. The reaction was purified using a G-25 column (GE health, 28922529). For the pulldown cells were washed with PBS and then incubated with biotinylated protein(s) for 3 hr on ice.  After incubation the plates were washed 3x with PBS (Fresenius Kabi) and the cells were harvested in 1x Cell Lysis Buffer (Cell Signaling Technologies, 9803). After spinning the supernatant was incubated with Neutravidin beads (Pierce, 29201) for 1 hr at 4°C (rotating). Beads were washed 4x using lysis buffer and 3x using 50 mM ammonium bicarbonate (Sigma-Aldrich, 09830), with fresh LoBind tubes used for each wash (Eppendorf, 0030 108.116). The beads were resuspended in 250 µl of 50 mM ammonium bicarbonate with 250 ng of mass spec grade trypsin (Promega V5113), incubated overnight at 37°C (with agitation), after which peptides were recovered from the beads with a pre-washed 0.4 µm filter (Ultrafree MC HV, Millipore, UFC30HV00) and subjected to mass spectrometry analysis."],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["Peptides were desalted using StageTips and measured in an Orbitrap Fusion LUMOS (Thermo Fisher Scientific) trybrid mass spectrometer coupled to EASY-nLC 1200 system (Proxeon, Odense, Denmark). Three technical repeats were performed injecting 2%, 10% and 50% of the sample respectively. Digested peptides were separated using a 50 cm long fused silica emitter (FS360-75-15-N-5-C50, New Objective, Massachusetts, US) in-house packed with 1.9 μm C18-AQ beads (Reprospher-DE, Pur, Dr. Maisch, Ammerburch-Entringen, Germany) and heated to 50°C in a Column Oven for ESI/Nano Spray (Sonation, Germany). Peptides were separated by liquid chromatography using a gradient from 2% to 32% acetonitrile with 0.1% formic acid for 30 min followed by column re-conditioning for 22 minutes. A Lock Mass of 445.12003 (polysiloxane) was used for internal calibration. Data was acquired in a Data Dependent Acquisition (DDA) mode with a TopSpeed method with cycle time of 3 s with a scan range of 400-1500 m/z and resolutions of 120,000 and 30,000 for MS1 and MS2, respectively, using in both cases the Orbitrap as detector. For MS2, an isolation window of 1.2 m/z and an HCD collision energy of 32% was applied. Precursors with a charge of 1 and higher than 6 were excluded from triggering MS2 as well as previously analyzed precursors with a dynamic exclusion window of 10s."],"omics_type":["Proteomics"],"labhead":["Roman González-Prieto"],"instrument_platform":[""],"labhead_affiliation":["CABIMER - University of Sevilla"],"submission_type":["PARTIAL"],"species":["Mus Musculus (mouse)"],"submitter_mail":["roman.gonzalez@cabimer.es"],"publication":["10.1002/ADVS.75322"],"submitter_affiliation":["Andalusian Center for Regenerative Medicine and Cell Biology, CABIMER, University of Seville"],"submitter_country":["Spain"],"additional_accession":[]},"is_claimable":false,"name":"Mechanism of action of parasite TGFb antagonist via mouse (co-)receptors inspires creation of novel cell-type-specific TGFb modulators","description":"A murine parasite modulates host responses by secreting modular TGFβ mimics (TGMs). Among these, the agonist TGM1 consists of five distinct domains (D); D1/2, D3, and D4/5 interact with the host (co-)receptors TGFBR1, TGFBR2, and CD44, respectively. In contrast, antagonist TGM6 lacks the D1/2 domains that bind to TGFBR1 but retains thed3-TGFBR2  interaction. First, we found that TGM6 antagonize TGFb/SMAD signaling on mice but not on human cells, with the amino acid differences in the extracellular domain of TGFBR2 being responsible for this disparity. Next, we demonstrated that TGM6 competes with TGFβ for its interaction with mouse TGFBR. Importantly, we identified using biochemical assays that betaglycan and low-density lipoprotein receptor-related protein 1 (LRP1) act as TGM6 co-receptors. The D4/5 domains of TGM6 interact with LRP1, while betaglycan requires TGFBR2 for effective binding to TGM6-D3. Through genetic misexpression and cell biological experiments, we showed that LRP1 is essential for cell-specific antagonism by TGM6, while betaglycan counteracts TGM6's function. The modular structure of TGMs enabled us to create chimeras of TGM1 and TGM6, thereby changing TGM6 cell-type specificity and converting the antagonist into an agonist.","dates":{"publication":"2026-04-15","submission":"2025-06-16"},"accession":"PXD065047","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:625351","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:1590","NEWT:10034","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:376619","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:1589","NEWT:135622","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:1582","NEWT:36630","NEWT:383379","NEWT:418106","NCBITaxon:12721","NEWT:10029","NEWT:913645","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:7719","NEWT:868565","NEWT:135674","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:224308","NEWT:3347","NEWT:160621","NEWT:212790","NEWT:110368","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:410658","NEWT:44688","NEWT:44689","NEWT:498211","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:44685","NEWT:161934","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:410661","NEWT:1140","NCBITaxon:2157","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:150808","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:3714","NEWT:270643","NEWT:2065263","NEWT:177437","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:28174","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:176597","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2499525","NEWT:2853422","NEWT:487","NEWT:1538553","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:1502","NEWT:128017","NEWT:376686","NEWT:237610","NEWT:95486","NEWT:1883446","NEWT:1233435","NEWT:118223","NEWT:11757","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:491","NEWT:460523","NEWT:45954","NEWT:235443","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:108458","NEWT:5936","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:1255228","NEWT:410289","NEWT:373153","NEWT:1640278","NEWT:472","NEWT:940825","NEWT:529507","NEWT:1071661","NEWT:28128","NEWT:470","NEWT:5911","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:33952","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:215402","NEWT:1547","NEWT:906914","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:3728","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:5180","NEWT:256737","NEWT:9541","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:2903","NEWT:185579","NEWT:13076","NEWT:207340","NEWT:1006581","NEWT:8673","NEWT:33940","NEWT:550","NEWT:554","NEWT:451516","NEWT:552","NEWT:1325291","NEWT:36185","NEWT:1054211","NEWT:1225786","NEWT:771870","NEWT:51338","NEWT:575412","NEWT:28112","NEWT:6493","NEWT:10832","NEWT:6494","NEWT:6491","NEWT:507601","NEWT:520","NEWT:186441","NEWT:643680","NEWT:214092","NCBITaxon:6157","NEWT:13095","NEWT:162425","NEWT:104105","NEWT:216257","NEWT:9986","NEWT:8654","NEWT:8658","NEWT:1268063","NEWT:8657","NEWT:9983","NEWT:8655","NEWT:5147","NEWT:28108","NEWT:28104","NEWT:407821","NEWT:568703","NCBITaxon:2","NEWT:568708","NEWT:1613","NEWT:986","NEWT:52641","NEWT:28532","NEWT:353152","NEWT:298176","NEWT:353153","NEWT:227377","NEWT:1774284","NEWT:40674","NEWT:1194669","NEWT:443906","NEWT:519","NEWT:2510939","NEWT:7394","NEWT:6063","NEWT:1328388","NEWT:105487","NEWT:1548728","NEWT:667127","NEWT:9557","NEWT:377586","NEWT:300641","NEWT:39655","NEWT:9554","NEWT:38323","NEWT:475932","NEWT:256318","NEWT:206411","NCBITaxon:6191","NEWT:229533","NEWT:214053","NEWT:28550","NEWT:80863","NEWT:90675","NEWT:52639","NEWT:52638","NEWT:57075","NEWT:1666905","NEWT:8697","NEWT:8695","NEWT:884204","NEWT:1045775","NEWT:1123869","NEWT:9544","NEWT:9545","NEWT:979","NEWT:7370","NEWT:83906","NEWT:99488","NEWT:1134506","NEWT:255470","NEWT:38783","NEWT:6426","NEWT:33090","NEWT:9935","NEWT:287889","NEWT:3059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