7POJ

Prodomain bound BMP10 crystal form 2

7POJ の概要

• エントリーDOI: 10.2210/pdb7poj/pdb
• 分子名称: Bone morphogenetic protein 10, TETRAETHYLENE GLYCOL, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: bmp10 bone morphogenetic protein prodomain tgfbeta signalling, cytokine
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 92618.01

構造登録者

Guo, J.,Yu, M.,Li, W. (登録日: 2021-09-09, 公開日: 2022-05-11, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.5 Å)