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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.date.accessioned2022-08-24T08:21:30Z
dc.date.available2022-08-24T08:21:30Z
dc.date.issued2022-05-03
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/340393
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.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleCrystal structures of BMPRII extracellular domain in binary and ternary receptor complexes with BMP10.
dc.typeArticle
dc.publisher.departmentDepartment of Medicine
dc.date.updated2022-04-13T13:36:55Z
prism.publicationNameNat Commun
dc.identifier.doi10.17863/CAM.87831
dcterms.dateAccepted2022-04-12
rioxxterms.versionofrecord10.1038/s41467-022-30111-2
rioxxterms.versionVoR
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]
dc.identifier.eissn2041-1723
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)
cam.depositDate2022-04-13
pubs.licence-identifierapollo-deposit-licence-2-1
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