PubMed:10880444 JSONTXT

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":0,"end":99},"obj":"Sentence"},{"id":"T2","span":{"begin":100,"end":261},"obj":"Sentence"},{"id":"T3","span":{"begin":262,"end":477},"obj":"Sentence"},{"id":"T4","span":{"begin":478,"end":664},"obj":"Sentence"},{"id":"T5","span":{"begin":665,"end":772},"obj":"Sentence"},{"id":"T6","span":{"begin":773,"end":895},"obj":"Sentence"},{"id":"T7","span":{"begin":896,"end":977},"obj":"Sentence"},{"id":"T8","span":{"begin":978,"end":1177},"obj":"Sentence"},{"id":"T9","span":{"begin":1178,"end":1314},"obj":"Sentence"}],"text":"BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II.\nBone morphogenetic protein-2 (BMP-2) induces bone formation and regeneration in adult vertebrates and regulates important developmental processes in all animals. BMP-2 is a homodimeric cysteine knot protein that, as a member of the transforming growth factor-beta (TGF-beta) superfamily, signals by oligomerizing type I and type II receptor serine-kinases in the cell membrane. The binding epitopes of BMP-2 for BMPR-IA (type I) and BMPR-II or ActR-II (type II) were characterized using BMP-2 mutant proteins for analysis of interactions with receptor ectodomains. A large epitope 1 for high-affinity BMPR-IA binding was detected spanning the interface of the BMP-2 dimer. A smaller epitope 2 for the low-affinity binding of BMPR-II was found to be assembled by determinants of a single monomer. Symmetry-related pairs of the two juxtaposed epitopes occur near the BMP-2 poles. Mutations in both epitopes yielded variants with reduced biological activity in C2C12 cells; however, only epitope 2 variants behaved as antagonists partially or completely inhibiting BMP-2 activity. These findings provide a framework for the molecular description of receptor recognition and activation in the BMP/TGF-beta superfamily."}

{"project":"FSU-PRGE","denotations":[{"id":"T1","span":{"begin":0,"end":5},"obj":"protein"},{"id":"T2","span":{"begin":91,"end":98},"obj":"protein"},{"id":"T3","span":{"begin":100,"end":128},"obj":"protein"},{"id":"T4","span":{"begin":130,"end":135},"obj":"protein"},{"id":"T5","span":{"begin":262,"end":267},"obj":"protein"},{"id":"T6","span":{"begin":332,"end":386},"obj":"protein"},{"id":"T7","span":{"begin":413,"end":455},"obj":"protein"},{"id":"T8","span":{"begin":502,"end":507},"obj":"protein"},{"id":"T9","span":{"begin":512,"end":519},"obj":"protein"},{"id":"T10","span":{"begin":533,"end":540},"obj":"protein"},{"id":"T11","span":{"begin":544,"end":551},"obj":"protein"},{"id":"T12","span":{"begin":587,"end":592},"obj":"protein"},{"id":"T13","span":{"begin":701,"end":708},"obj":"protein"},{"id":"T14","span":{"begin":760,"end":765},"obj":"protein"},{"id":"T15","span":{"begin":825,"end":832},"obj":"protein"},{"id":"T16","span":{"begin":965,"end":970},"obj":"protein"},{"id":"T17","span":{"begin":1162,"end":1167},"obj":"protein"},{"id":"T18","span":{"begin":1289,"end":1313},"obj":"protein"}],"text":"BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II.\nBone morphogenetic protein-2 (BMP-2) induces bone formation and regeneration in adult vertebrates and regulates important developmental processes in all animals. BMP-2 is a homodimeric cysteine knot protein that, as a member of the transforming growth factor-beta (TGF-beta) superfamily, signals by oligomerizing type I and type II receptor serine-kinases in the cell membrane. The binding epitopes of BMP-2 for BMPR-IA (type I) and BMPR-II or ActR-II (type II) were characterized using BMP-2 mutant proteins for analysis of interactions with receptor ectodomains. A large epitope 1 for high-affinity BMPR-IA binding was detected spanning the interface of the BMP-2 dimer. A smaller epitope 2 for the low-affinity binding of BMPR-II was found to be assembled by determinants of a single monomer. Symmetry-related pairs of the two juxtaposed epitopes occur near the BMP-2 poles. Mutations in both epitopes yielded variants with reduced biological activity in C2C12 cells; however, only epitope 2 variants behaved as antagonists partially or completely inhibiting BMP-2 activity. These findings provide a framework for the molecular description of receptor recognition and activation in the BMP/TGF-beta superfamily."}

{"project":"AIMed","denotations":[{"id":"T1","span":{"begin":0,"end":5},"obj":"protein"},{"id":"T2","span":{"begin":91,"end":98},"obj":"protein"},{"id":"T3","span":{"begin":101,"end":128},"obj":"protein"},{"id":"T4","span":{"begin":130,"end":135},"obj":"protein"},{"id":"T5","span":{"begin":262,"end":267},"obj":"protein"},{"id":"T6","span":{"begin":332,"end":363},"obj":"protein"},{"id":"T7","span":{"begin":365,"end":373},"obj":"protein"},{"id":"T8","span":{"begin":502,"end":507},"obj":"protein"},{"id":"T9","span":{"begin":512,"end":519},"obj":"protein"},{"id":"T10","span":{"begin":533,"end":540},"obj":"protein"},{"id":"T11","span":{"begin":544,"end":551},"obj":"protein"},{"id":"T12","span":{"begin":587,"end":592},"obj":"protein"},{"id":"T13","span":{"begin":701,"end":708},"obj":"protein"},{"id":"T14","span":{"begin":760,"end":765},"obj":"protein"},{"id":"T15","span":{"begin":825,"end":832},"obj":"protein"},{"id":"T16","span":{"begin":965,"end":970},"obj":"protein"},{"id":"T17","span":{"begin":1162,"end":1167},"obj":"protein"},{"id":"T18","span":{"begin":1293,"end":1301},"obj":"protein"}],"text":"BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II.\nBone morphogenetic protein-2 (BMP-2) induces bone formation and regeneration in adult vertebrates and regulates important developmental processes in all animals. BMP-2 is a homodimeric cysteine knot protein that, as a member of the transforming growth factor-beta (TGF-beta) superfamily, signals by oligomerizing type I and type II receptor serine-kinases in the cell membrane. The binding epitopes of BMP-2 for BMPR-IA (type I) and BMPR-II or ActR-II (type II) were characterized using BMP-2 mutant proteins for analysis of interactions with receptor ectodomains. A large epitope 1 for high-affinity BMPR-IA binding was detected spanning the interface of the BMP-2 dimer. A smaller epitope 2 for the low-affinity binding of BMPR-II was found to be assembled by determinants of a single monomer. Symmetry-related pairs of the two juxtaposed epitopes occur near the BMP-2 poles. Mutations in both epitopes yielded variants with reduced biological activity in C2C12 cells; however, only epitope 2 variants behaved as antagonists partially or completely inhibiting BMP-2 activity. These findings provide a framework for the molecular description of receptor recognition and activation in the BMP/TGF-beta superfamily."}