ArticleActa crystallographica. Section D, Biological crystallography2014
Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex.
Article in Acta crystallographica. Section D, Biological crystallography, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- State of the Science on Brain Insulin Resistance and Cognitive Decline Due to Alzheimer's Disease.Aging and disease · 2024Review
- Non-glycosylated IGF2 prohormones are more mitogenic than native IGF2.Communications biology · 2023Article
- Molecular Aspects of Insulin Aggregation and Various Therapeutic Interventions.ACS bio & med chem Au · 2022Review
- Progress in Simulation Studies of Insulin Structure and Function.Frontiers in endocrinology · 2022Review
- Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques.Scientific reports · 2021Article
- 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
- Insulin and Insulin Receptors in Adipose Tissue Development.International journal of molecular sciences · 2019Review
- A versatile insulin analog with high potency for both insulin and insulin-like growth factor 1 receptors: Structural implications for receptor binding.The Journal of biological chemistry · 2018Article
- Insulin Receptor Isoforms in Physiology and Disease: An Updated View.Endocrine reviews · 2017Review
- Computational study of the activity, dynamics, energetics and conformations of insulin analogues using molecular dynamics simulations: Application to hyperinsulinemia and the critical residue B26.Biochemistry and biophysics reports · 2017Article
- Structural Perspectives of Insulin Receptor Isoform-Selective Insulin Analogs.Frontiers in endocrinology · 2017Article
- Probing Receptor Specificity by Sampling the Conformational Space of the Insulin-like Growth Factor II C-domain.The Journal of biological chemistry · 2016Article
- Contribution of TyrB26 to the Function and Stability of Insulin: STRUCTURE-ACTIVITY RELATIONSHIPS AT A CONSERVED HORMONE-RECEPTOR INTERFACE.The Journal of biological chemistry · 2016Article
- Rational steering of insulin binding specificity by intra-chain chemical crosslinking.Scientific reports · 2016Article
- Elucidating the Activation Mechanism of the Insulin-Family Proteins with Molecular Dynamics Simulations.PloS one · 2016Article
- Molecular Dynamics Simulations of Insulin: Elucidating the Conformational Changes that Enable Its Binding.PloS one · 2015Article
- Structural and functional study of the GlnB22-insulin mutant responsible for maturity-onset diabetes of the young.PloS one · 2014Article
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8 authors.
Funding
Abstract
The structural characterization of the insulin-insulin receptor (IR) interaction still lacks the conformation of the crucial B21-B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms.
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