ArticleeLife2024
Structural dynamics of the active HER4 and HER2/HER4 complexes is finely tuned by different growth factors and glycosylation.
Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Review
- Differential ErbB receptor dimerization modulates the ability of EGF receptor ligands to regulate metabolic flux.The Journal of biological chemistry · 2026Article
- Recurrent cancer-associated ERBB4 mutations are transforming and confer resistance to targeted therapies.Molecular oncology · 2026Article
- RET receptor tyrosine kinase architecture, assemblies, and activation.Endocrine-related cancer · 2026Review
- The role of kinase domain dimerization in EGFR activation.Structure (London, England : 1993) · 2026Article
- Real-Time Therapy Response Monitoring Using Surface Biomarkers on Circulating Tumor Cells.Cancers · 2026Review
- Lipids regulate epidermal growth factor receptor activation by its ligands.Biochemical Society transactions · 2026Review
- Functional Suitability Evaluation of Radioimmunoconjugates of Nanobodies against PD-L1 and HER2/neu for Tumor Theranostics.Sovremennye tekhnologii v meditsine · 2026Article
- Inhibition of HER2 signaling and breast cancer cell growth with a novel antibody targeting HER2 ECD III/IV.PloS one · 2026Article
- Regulation of receptor tyrosine kinase hetero-interactions.Current opinion in structural biology · 2025Review
- Structural analysis of HER2-trastuzumab complex reveals receptor conformational adaptation.Science advances · 2025Article
- Structure and organization of full-length epidermal growth factor receptor in extracellular vesicles by cryo-electron tomography.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- HER4 is a high-affinity dimerization partner for all EGFR/HER/ErbB family proteins.Protein science : a publication of the Protein Society · 2024Article
- Review
Corrections and comments
- Update of
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Human Epidermal growth factor Receptor 4 (HER4 or ERBB4) carries out essential functions in the development and maintenance of the cardiovascular and nervous systems. HER4 activation is regulated by a diverse group of extracellular ligands including the neuregulin (NRG) family and betacellulin (BTC), which promote HER4 homodimerization or heterodimerization with other HER receptors. Important cardiovascular functions of HER4 are exerted via heterodimerization with its close homolog and orphan receptor, HER2. To date structural insights into ligand-mediated HER4 activation have been limited to crystallographic studies of HER4 ectodomain homodimers in complex with NRG1β. Here, we report cryo-EM structures of near full-length HER2/HER4 heterodimers and full-length HER4 homodimers bound to NRG1β and BTC. We show that the structures of the heterodimers bound to either ligand are nearly identical and that in both cases the HER2/HER4 heterodimer interface is less dynamic than those observed in structures of HER2/EGFR and HER2/HER3 heterodimers. In contrast, structures of full-length HER4 homodimers bound to NRG1β and BTC display more large-scale dynamics mirroring states previously reported for EGFR homodimers. Our structures also reveal the presence of multiple glycan modifications within HER4 ectodomains, modeled for the first time in HER receptors, that distinctively contribute to the stabilization of HER4 homodimer interfaces over those of HER2/HER4 heterodimers.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.