Tyrosine kinase receptor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) bind to hormones, such as insulin, IGF-1, and IGF-2, and transduces the signals across the cell membrane. However, the complete structure of the receptor and the signal transduction mechanism remains unclear. Here, we report the cryo-EM structure of the ligand-bound ectodomain in the full-length human IGF-1R. We reconstructed the IGF-1R/insulin complex at 4.7 Å and the IGF-1R/IGF-1 complex at 7.7 Å. Our structures reveal that only one insulin or one IGF-1 molecule binds to and activates the full-length human IGF-1R receptor.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.str.2020.03.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.
Background: Reversible post-translational modifications, phosphorylation and dephosphorylation, on tau protein play a critical role in the microtubule (MT) modulation. However, abnormal tau phosphorylation, which occurs in tauopathies such as Alzheimer's disease (AD), causes the dissociation of tau from MTs. The dissociated tau then aggregates into sequent forms from soluble oligomers to paired helical filaments (PHF), and insoluble neurofibrillary tangles (NFTs), a hallmark of AD.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Cleveland Clinic, Cleveland, OH, USA.
Background: Apolipoprotein E (ApoE) is the primary cholesterol and lipid transporting apolipoprotein in the central nervous system (CNS) and is the greatest genetic risk factor for Alzheimer's Disease (AD). There are three main isoforms differing by single amino acid changes: ε3 is "neutral", ε4 is "risk" (Cys112Arg), and ε2 is "resilience" (Arg158Cys). Rare forms (Christchurch, Jacksonville) have also been proposed as resilience alleles, while an ε4-like allele (with Arg61Thr) is present in non-human primates without AD risk.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Connecticut, Storrs, CT, USA.
Background: With insight into the elevated levels of phosphorylation of diseased tau, it is believed that specific modifications occur in a time-dependent manner that contribute to tau's role in Alzheimer's disease pathogenesis and progression. Present methods to obtain phospho-tau (p-tau) from post-mortem tissue or recombinantly are insufficient to answer the foremost questions in the field, and there is currently no way to study each disease-relevant modification reproducibly or in isolation. To this point, learning about tau phosphorylation at the resolution of a single modification has been a major obstacle in clarifying whether certain sites are causative of disease or just a by-product of other harmful mechanisms.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of Kansas Medical Center, Kansas City, KS, USA.
Background: Mitochondrial dysfunction and Aβ accumulation are hallmarks of Alzheimer's disease (AD). However, the role of these pathologies in Down Syndrome associated Alzheimer's Disease (DSAD) is unknown. Decades of research describe a relationship between mitochondrial function and Aβ production.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Background: Alzheimer's disease (AD) hallmarks are amyloid plaques and tau tangles. APOE and TREM2 are the strongest genetic risk factors for AD. Triggering receptor expressed on myeloid cells 2 (TREM2) is increasingly recognized to play a central role in amyloid beta clearance and microglia activation in AD.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!