|
|
|
|
LEADER |
01864nam a2200253Ia 4500 |
001 |
10.1038-s41467-022-30111-2 |
008 |
220706s2022 CNT 000 0 und d |
020 |
|
|
|a 20411723 (ISSN)
|
245 |
1 |
0 |
|a Crystal structures of BMPRII extracellular domain in binary and ternary receptor complexes with BMP10
|
260 |
|
0 |
|b Nature Research
|c 2022
|
856 |
|
|
|z View Fulltext in Publisher
|u https://doi.org/10.1038/s41467-022-30111-2
|
520 |
3 |
|
|a 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. © 2022, The Author(s).
|
700 |
1 |
0 |
|a Guo, J.
|e author
|
700 |
1 |
0 |
|a Li, W.
|e author
|
700 |
1 |
0 |
|a Li, X.
|e author
|
700 |
1 |
0 |
|a Liu, B.
|e author
|
700 |
1 |
0 |
|a Morrell, N.W.
|e author
|
700 |
1 |
0 |
|a Read, R.J.
|e author
|
700 |
1 |
0 |
|a Salmon, R.M.
|e author
|
700 |
1 |
0 |
|a ten Dijke, P.
|e author
|
700 |
1 |
0 |
|a Thorikay, M.
|e author
|
700 |
1 |
0 |
|a Tong, Z.
|e author
|
700 |
1 |
0 |
|a Yu, M.
|e author
|
773 |
|
|
|t Nature Communications
|