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Crystal structures of BMPRII extracellular domain in binary and ternary receptor complexes with BMP10.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Liu, Bin 
Thorikay, Midory 
Li, Xiaoyan 

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.

Description

Keywords

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

Publisher

Nature Research
Sponsorship
British Heart Foundation (None)
British Heart Foundation (PG/17/1/32532)
British Heart Foundation (FS/SBSRF/20/31005)
British Heart Foundation (FS/4yPhD/F/20/34124B)