ArticleThe Journal of biological chemistry2016
Probing Receptor Specificity by Sampling the Conformational Space of the Insulin-like Growth Factor II C-domain.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Regulation and function of insulin and insulin-like growth factor receptor signalling.Nature reviews. Molecular cell biology · 2025Review
- Activation of the insulin receptor by insulin-like growth factor 2.Nature communications · 2024Article
- The final walk with preptin.PloS one · 2024Article
- Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2.Communications biology · 2023Article
- Recombinant Insulin-Like Growth Factor 1 Dimers: Receptor Binding Affinities and Activation Abilities.International journal of peptide research and therapeutics · 2023Article
- Insulin-like Growth Factor-2 (IGF-2) in Fibrosis.Biomolecules · 2022Review
- Determinants of IGF-II influencing stability, receptor binding and activation.Scientific reports · 2022Article
- How IGF-II Binds to the Human Type 1 Insulin-like Growth Factor Receptor.Structure (London, England : 1993) · 2020Article
- Article
- Mutations at hypothetical binding site 2 in insulin and insulin-like growth factors 1 and 2 result in receptor- and hormone-specific responses.The Journal of biological chemistry · 2019Article
- Cross-Linking/Mass Spectrometry Uncovers Details of Insulin-Like Growth Factor Interaction With Insect Insulin Binding Protein Imp-L2.Frontiers in endocrinology · 2019Article
- Structural Perspectives of Insulin Receptor Isoform-Selective Insulin Analogs.Frontiers in endocrinology · 2017Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin and insulin-like growth factors I and II are closely related protein hormones. Their distinct evolution has resulted in different yet overlapping biological functions with insulin becoming a key regulator of metabolism, whereas insulin-like growth factors (IGF)-I/II are major growth factors. Insulin and IGFs cross-bind with different affinities to closely related insulin receptor isoforms A and B (IR-A and IR-B) and insulin-like growth factor type I receptor (IGF-1R). Identification of structural determinants in IGFs and insulin that trigger their specific signaling pathways is of increasing importance in designing receptor-specific analogs with potential therapeutic applications. Here, we developed a straightforward protocol for production of recombinant IGF-II and prepared six IGF-II analogs with IGF-I-like mutations. All modified molecules exhibit significantly reduced affinity toward IR-A, particularly the analogs with a Pro-Gln insertion in the C-domain. Moreover, one of the analogs has enhanced binding affinity for IGF-1R due to a synergistic effect of the Pro-Gln insertion and S29N point mutation. Consequently, this analog has almost a 10-fold higher IGF-1R/IR-A binding specificity in comparison with native IGF-II. The established IGF-II purification protocol allowed for cost-effective isotope labeling required for a detailed NMR structural characterization of IGF-II analogs that revealed a link between the altered binding behavior of selected analogs and conformational rearrangement of their C-domains.
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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.