5U8Q

Structure of the ectodomain of the human Type 1 insulin-like growth factor receptor in complex with IGF-I

Summary for 5U8Q

• Entry DOI: 10.2210/pdb5u8q/pdb
• Related: 5U8R
• Descriptor: Insulin-like growth factor 1 receptor, Insulin-like growth factor I, Fv 24-60 heavy chain, ... (9 entities in total)
• Functional Keywords: receptor tyrosine kinase, type 1 insulin-like growth factor receptor, insulin-like growth-factor i, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 137018.95

Authors

Lawrence, M.,Xu, Y. (deposition date: 2016-12-14, release date: 2018-02-28, Last modification date: 2024-10-23)

Primary citation

Xu, Y.,Kong, G.K.,Menting, J.G.,Margetts, M.B.,Delaine, C.A.,Jenkin, L.M.,Kiselyov, V.V.,De Meyts, P.,Forbes, B.E.,Lawrence, M.C.
How ligand binds to the type 1 insulin-like growth factor receptor.
Nat Commun, 9:821-821, 2018

PubMed Abstract: Human type 1 insulin-like growth factor receptor is a homodimeric receptor tyrosine kinase that signals into pathways directing normal cellular growth, differentiation and proliferation, with aberrant signalling implicated in cancer. Insulin-like growth factor binding is understood to relax conformational restraints within the homodimer, initiating transphosphorylation of the tyrosine kinase domains. However, no three-dimensional structures exist for the receptor ectodomain to inform atomic-level understanding of these events. Here, we present crystal structures of the ectodomain in apo form and in complex with insulin-like growth factor I, the latter obtained by crystal soaking. These structures not only provide a wealth of detail of the growth factor interaction with the receptor's primary ligand-binding site but also indicate that ligand binding separates receptor domains by a mechanism of induced fit. Our findings are of importance to the design of agents targeting IGF-1R and its partner protein, the human insulin receptor.

PubMed: 29483580
DOI: 10.1038/s41467-018-03219-7

Experimental method

X-RAY DIFFRACTION (3.27104018461 Å)