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dc.contributor.authorGuo, Jingxu
dc.contributor.authorLiu, Bin
dc.contributor.authorThorikay, Midory
dc.contributor.authorYu, Minmin
dc.contributor.authorLi, Xiaoyan
dc.contributor.authorTong, Zhen
dc.contributor.authorSalmon, Richard M
dc.contributor.authorRead, Randy
dc.contributor.authorTen Dijke, Peter
dc.contributor.authorMorrell, Nicholas
dc.contributor.authorLi, Wei
dc.description.abstractHeterozygous mutations in BMPR2 (bone morphogenetic protein (BMP) receptor type II) cause pulmonary arterial hypertension. BMPRII is a receptor for over 15 BMP ligands, but why BMPR2 mutations cause lung-specific pathology is unknown. To elucidate the molecular basis of BMP:BMPRII interactions, we report crystal structures of binary and ternary BMPRII receptor complexes with BMP10, which contain an ensemble of seven different BMP10:BMPRII 1:1 complexes. BMPRII binds BMP10 at the knuckle epitope, with the A-loop and β4 strand making BMPRII-specific interactions. The BMPRII binding surface on BMP10 is dynamic, and the affinity is weaker in the ternary complex than in the binary complex. Hydrophobic core and A-loop interactions are important in BMPRII-mediated signalling. Our data reveal how BMPRII is a low affinity receptor, implying that forming a signalling complex requires high concentrations of BMPRII, hence mutations will impact on tissues with highest BMPR2 expression such as the lung vasculature.
dc.publisherNature Research
dc.rightsAttribution 4.0 International
dc.titleCrystal structures of BMPRII extracellular domain in binary and ternary receptor complexes with BMP10.
dc.publisher.departmentDepartment of Medicine
prism.publicationNameNat Commun
dc.contributor.orcidGuo, Jingxu [0000-0002-1568-4842]
dc.contributor.orcidYu, Minmin [0000-0003-4442-7586]
dc.contributor.orcidSalmon, Richard M [0000-0001-6327-5341]
dc.contributor.orcidRead, Randy [0000-0001-8273-0047]
dc.contributor.orcidMorrell, Nicholas [0000-0001-5700-9792]
dc.contributor.orcidLi, Wei [0000-0002-1924-3120]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idBritish Heart Foundation (PG/17/1/32532)
pubs.funder-project-idBritish Heart Foundation (FS/SBSRF/20/31005)
pubs.funder-project-idBritish Heart Foundation (FS/4yPhD/F/20/34124B)
pubs.licence-display-nameApollo Repository Deposit Licence Agreement

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International