PXD067251

PXD067251 is an original dataset announced via ProteomeXchange.

Title	An engineered insulin analog with dual insulin and IGF-1 receptor agonism and distinct signaling
Description	Insulin and insulin-like growth factors (IGF-1 and IGF-2) regulate metabolism, growth, and development via related receptors. In contexts such as brain function or fetal development, coordinated signaling by all three hormones is essential. We report the engineering of [GluB10, D-HisB24, GlyB31, TyrB32]-insulin (1Ins), an analog with high affinity for IR-A, IR-B, and especially IGF-1R. 1Ins binds IGF-1R ~1,000-fold more strongly than native insulin, approaching IGF-1 levels. CryoEM structures reveal how minimal substitutions in 1Ins enable effective binding to both IR-A and IGF-1R. In neuronal cells, 1Ins robustly activates both IR and IGF-1R pathways, promotes survival, and exceeds native ligands in neuroprotective assays. In vivo, 1Ins regulates glucose effectively in mice and rats. Phosphoproteomic profiling confirms dual pathway activation and identifies targets unique to 1Ins. These findings demonstrate that rational design of dual-receptor agonists can yield potent, versatile ligands with therapeutic promise in metabolic control, neuroprotection, and regeneration.
HostingRepository	PRIDE
AnnounceDate	2026-04-09
AnnouncementXML	Submission_2026-04-09_07:33:33.332.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jana Brezinova
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-12 03:14:29	ID requested
⏵ 1	2026-04-09 07:33:33	announced

Dataset with its publication pending

submitter keyword: neuroblastoma, SH-SY5Y, insulin analog,human, LC-MS/MS

Jiri Jiracek
contact affiliation	Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo n. 2, 16610 Praha 6, Czech Republic
contact email	jiracek@uochb.cas.cz
lab head
Jana Brezinova
contact affiliation	Institute of Organic Chemistry and Biochemistry, Czech Academy of Science, Flemingovo n. 2, Prague, 166 10, Czech Republic
contact email	jana.brezinova@uochb.cas.cz
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD067251

PRIDE project URI

• PRIDE
  1. PXD067251
     1. Label: PRIDE project
     2. Name: An engineered insulin analog with dual insulin and IGF-1 receptor agonism and distinct signaling