{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T07:01:33Z","timestamp":1786863693647,"version":"build-2736575974"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Recombinant bone morphogenetic protein 2 (rhBMP2) has been used clinically to treat bone fractures in human patients. However, the high doses of rhBMP2 required for a therapeutic response can cause undesirable side effects. Here, we demonstrate that a novel Activin A\/BMP2 (AB2) chimera, AB204, promotes osteogenesis and bone healing much more potently and effectively than rhBMP2. Remarkably, 1 month of AB204 treatment completely heals tibial and calvarial defects of critical size in mice at a concentration 10-fold lower than a dose of rhBMP2 that only partially heals the defect. We determine the structure of AB204 to 2.3 \u00c5 that reveals a distinct BMP2-like fold in which the Activin A sequence segments confer insensitivity to the BMP2 antagonist Noggin and an affinity for the Activin\/BMP type II receptor ActRII that is 100-fold greater than that of BMP2. The structure also led to our identification of a single Activin A-derived amino acid residue, which, when mutated to the corresponding BMP2 residue, resulted in a significant increase in the affinity of AB204 for its type I receptor BMPRIa and a further enhancement in AB204's osteogenic potency. Together, these findings demonstrate that rationally designed AB2 chimeras can provide BMP2 substitutes with enhanced potency for treating non-union bone fractures. \u00a9 2014 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.2238","type":"journal-article","created":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T12:58:14Z","timestamp":1396357094000},"page":"1950-1959","source":"Crossref","is-referenced-by-count":40,"title":["An Activin A\/BMP2 Chimera, AB204, Displays Bone-Healing Properties Superior to Those of BMP2"],"prefix":"10.1093","volume":"29","author":[{"given":"Byung-Hak","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of PharmacologySeoul National University College of MedicineSeoulRepublic of Korea"},{"name":"Protein Engineering LaboratoryJoint Center for Biosciences at Songdo Global University CampusIncheonRepublic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Esquivies","sequence":"additional","affiliation":[{"name":"Structural Biology LaboratoryThe Salk Institute for Biological StudiesLa JollaCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihoon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Protein Engineering LaboratoryJoint Center for Biosciences at Songdo Global University CampusIncheonRepublic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C","family":"Gray","sequence":"additional","affiliation":[{"name":"Clayton Foundation Laboratories for Peptide BiologySalk Institute for Biological StudiesLa JollaCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-kyu","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of PharmacologySeoul National University College of MedicineSeoulRepublic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Witek","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Structural Biology LaboratoryThe Salk Institute for Biological StudiesLa JollaCAUSA"},{"name":"Protein Engineering LaboratoryJoint Center for Biosciences at Songdo Global University CampusIncheonRepublic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senyon","family":"Choe","sequence":"additional","affiliation":[{"name":"Structural Biology LaboratoryThe Salk Institute for Biological StudiesLa JollaCAUSA"},{"name":"Protein Engineering LaboratoryJoint Center for Biosciences at Songdo Global University CampusIncheonRepublic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,4,1]]},"reference":[{"issue":"3698","key":"2024020318490422400_jbmr2238-bib-0001","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1126\/science.150.3698.893","article-title":"Bone: formation by autoinduction","volume":"150","author":"Urist","year":"1965","journal-title":"Science."},{"issue":"2","key":"2024020318490422400_jbmr2238-bib-0002","doi-asserted-by":"crossref","first-page":"272","DOI":"10.7150\/ijbs.2929","article-title":"TGF-\u03b2 and BMP signaling in osteoblast differentiation and bone formation","volume":"8","author":"Chen","year":"2012","journal-title":"Int J Biol Sci."},{"issue":"5","key":"2024020318490422400_jbmr2238-bib-0003","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1517\/14712598.4.5.741","article-title":"The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in orthopaedic 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