title: Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain.
abstract: Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. However, only a low-resolution (3.8 Å) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding.
authors: Institute of Health and Biomedical Innovation, Queensland University of Technology, QLD 4059, Australia.
authors: Tristan I
authors: TI
authors: Croll
authors: La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia.
authors: Brian J
authors: BJ
authors: Smith
authors: Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors: Mai B
authors: MB
authors: Margetts
authors: Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Jonathan
authors: J
authors: Whittaker
authors: Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA; Departments of Physiology, and Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Michael A
authors: MA
authors: Weiss
authors: Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors: Colin W
authors: CW
authors: Ward
authors: Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: lawrence@wehi.edu.au.
authors: Michael C
authors: MC
authors: Lawrence
mesh_terms: D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011972:Receptor, Insulin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D005353:Fibronectins; C435941:INSR protein, human; D011972:Receptor, Insulin