ArticleNature communications2023
A blocking monoclonal antibody reveals dimerization of intracellular domains of ALK2 associated with genetic disorders.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- First-In-Human Study to Assess the Pharmacokinetics and Safety of DS-6016a After Single Subcutaneous Injection in Healthy Japanese Adults.Clinical pharmacology in drug development · 2026Trial
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- Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva.Journal of Zhejiang University. Science. B · 2025Review
- Sex as a Critical Variable in Basic and Pre-Clinical Studies of Fibrodysplasia Ossificans Progressiva.Biomolecules · 2024Article
- Article
- How Activin A Became a Therapeutic Target in Fibrodysplasia Ossificans Progressiva.Biomolecules · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in activin receptor-like kinase 2 (ALK2) can cause the pathological osteogenic signaling seen in some patients with fibrodysplasia ossificans progressiva and other conditions such as diffuse intrinsic pontine glioma. Here, we report that intracellular domain of wild-type ALK2 readily dimerizes in response to BMP7 binding to drive osteogenic signaling. This osteogenic signaling is pathologically triggered by heterotetramers of type II receptor kinases and ALK2 mutant forms, which form intracellular domain dimers in response to activin A binding. We develop a blocking monoclonal antibody, Rm0443, that can suppress ALK2 signaling. We solve the crystal structure of the ALK2 extracellular domain complex with a Fab fragment of Rm0443 and show that Rm0443 induces dimerization of ALK2 extracellular domains in a back-to-back orientation on the cell membrane by binding the residues H64 and F63 on opposite faces of the ligand-binding site. Rm0443 could prevent heterotopic ossification in a mouse model of fibrodysplasia ossificans progressiva that carries the human R206H pathogenic mutant.
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Registered trials
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