6unp

<table><tr><td colspan='2'>[[6unp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UNP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UNP FirstGlance]. <br>

== Disease ==

[https://www.uniprot.org/uniprot/BMPR2_HUMAN BMPR2_HUMAN] Defects in BMPR2 are the cause of primary pulmonary hypertension (PPH1) [MIM:[https://omim.org/entry/178600 178600]. PPH1 is a rare autosomal dominant disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial PPH1 is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.<ref>PMID:10903931</ref> <ref>PMID:11015450</ref> <ref>PMID:10973254</ref> <ref>PMID:11115378</ref> <ref>PMID:12358323</ref> <ref>PMID:15965979</ref> Defects in BMPR2 are a cause of pulmonary venoocclusive disease (PVOD) [MIM:[https://omim.org/entry/265450 265450]. PVOD is a rare form of pulmonary hypertension in which the vascular changes originate in the small pulmonary veins and venules. The pathogenesis is unknown and any link with PPH1 has been speculative. The finding of PVOD associated with a BMPR2 mutation reveals a possible pathogenetic connection with PPH1.<ref>PMID:12446270</ref> <ref>PMID:16429395</ref>

== Function ==

[https://www.uniprot.org/uniprot/BMPR2_HUMAN BMPR2_HUMAN] On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Binds to BMP-7, BMP-2 and, less efficiently, BMP-4. Binding is weak but enhanced by the presence of type I receptors for BMPs.

<div style="background-color:#fffaf0;">

== Publication Abstract from PubMed ==

Upon ligand binding, bone morphogenetic protein (BMP) receptors form active tetrameric complexes, comprised of two type I and two type II receptors, which then transmit signals to SMAD proteins. The link between receptor tetramerization and the mechanism of kinase activation, however, has not been elucidated. Here, using hydrogen deuterium exchange mass spectrometry (HDX-MS), small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, combined with analysis of SMAD signaling, we show that the kinase domain of the type I receptor ALK2 and type II receptor BMPR2 form a heterodimeric complex via their C-terminal lobes. Formation of this dimer is essential for ligand-induced receptor signaling and is targeted by mutations in BMPR2 in patients with pulmonary arterial hypertension (PAH). We further show that the type I/type II kinase domain heterodimer serves as the scaffold for assembly of the active tetrameric receptor complexes to enable phosphorylation of the GS domain and activation of SMADs.

Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization.,Agnew C, Ayaz P, Kashima R, Loving HS, Ghatpande P, Kung JE, Underbakke ES, Shan Y, Shaw DE, Hata A, Jura N Nat Commun. 2021 Aug 16;12(1):4950. doi: 10.1038/s41467-021-25248-5. PMID:34400635<ref>PMID:34400635</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

</div>

<div class="pdbe-citations 6unp" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Homo sapiens]]