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Biophysical and structural investigation of CRBN has been limited by current constructs that either require co-expression with the adaptor DDB1 or inadequately represent full-length protein, with high-resolution structures of degrader ternary complexes remaining rare. We present the design of CRBN\n                    <jats:sup>midi<\/jats:sup>\n                    , a construct that readily expresses from\n                    <jats:italic>E. coli<\/jats:italic>\n                    with high yields as soluble, stable protein without DDB1. We benchmark CRBN\n                    <jats:sup>midi<\/jats:sup>\n                    for wild-type functionality through a suite of biophysical techniques and solve high-resolution co-crystal structures of its binary and ternary complexes with degraders. We qualify CRBN\n                    <jats:sup>midi<\/jats:sup>\n                    as an enabling tool to accelerate structure-based discovery of the next generation of CRBN based therapeutics.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-52871-9","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T10:43:21Z","timestamp":1728989001000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Design of a Cereblon construct for crystallographic and biophysical studies of protein degraders"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4166-1270","authenticated-orcid":false,"given":"Alena","family":"Kroupova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina A.","family":"Spiteri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe J.","family":"Rutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotake","family":"Furihata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7012-3486","authenticated-orcid":false,"given":"Darren","family":"Darren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0922-9448","authenticated-orcid":false,"given":"Sarath","family":"Ramachandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4591-2658","authenticated-orcid":false,"given":"Sohini","family":"Chakraborti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5025-3821","authenticated-orcid":false,"given":"Kevin","family":"Haubrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Pethe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denzel","family":"Gonzales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre J.","family":"Wijaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2434-1603","authenticated-orcid":false,"given":"Maria","family":"Rodriguez-Rios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4026-2211","authenticated-orcid":false,"given":"Manon","family":"Sturbaut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6245-9704","authenticated-orcid":false,"given":"Dylan M.","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8610-932X","authenticated-orcid":false,"given":"William","family":"Farnaby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1362-191X","authenticated-orcid":false,"given":"Mark A.","family":"Nakasone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7613-2013","authenticated-orcid":false,"given":"David","family":"Zollman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8654-1670","authenticated-orcid":false,"given":"Alessio","family":"Ciulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"52871_CR1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","volume":"21","author":"M B\u00e9k\u00e9s","year":"2022","unstructured":"B\u00e9k\u00e9s, M., Langley, D. 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