7PPC

Ternary signalling complex of BMP10 bound to ALK1 and BMPRII

Summary for 7PPC

• Entry DOI: 10.2210/pdb7ppc/pdb
• Descriptor: Bone morphogenetic protein 10, Serine/threonine-protein kinase receptor R3, Bone morphogenetic protein receptor type-2, ... (4 entities in total)
• Functional Keywords: bmprii bmp10 alk1 signalling complex, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 147266.30

Authors

Guo, J.,Yu, M.,Read, R.J.,Li, W. (deposition date: 2021-09-13, release date: 2022-05-11, Last modification date: 2024-10-23)

Primary citation

Guo, J.,Liu, B.,Thorikay, M.,Yu, M.,Li, X.,Tong, Z.,Salmon, R.M.,Read, R.J.,Ten Dijke, P.,Morrell, N.W.,Li, W.
Crystal structures of BMPRII extracellular domain in binary and ternary receptor complexes with BMP10.
Nat Commun, 13:2395-2395, 2022

PubMed Abstract: Heterozygous 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.

PubMed: 35504921
DOI: 10.1038/s41467-022-30111-2

Experimental method

X-RAY DIFFRACTION (3.6 Å)