Solution structure of human insulin‐like growth factor II; recognition sites for receptors and binding proteins

• Published in: The EMBO journal 1994-12, Vol.13 (23), p.5590-5597
• Main Authors: Terasawa, H., Kohda, D., Hatanaka, H., Nagata, K., Higashihashi, N., Fujiwara, H., Sakano, K., Inagaki, F.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Carrier Proteins - metabolism; Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor II - chemistry; Insulin-Like Growth Factor II - metabolism; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Protein Binding; Protein Conformation; Receptor, IGF Type 2 - metabolism; Sequence Alignment; Solutions
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1994.tb06896.x

The three‐dimensional structure of human insulin‐like growth factor II was determined at high resolution in aqueous solution by NMR and simulated annealing based calculations. The structure is quite similar to those of insulin and insulin‐like growth factor I, which consists of an alpha‐helix followed by a turn and a strand in the B‐region and two antiparallel alpha‐helices in the A‐region. However, the regions of Ala1‐Glu6, Pro31‐Arg40 and Thr62‐Glu67 are not well‐defined for lack of distance constraints, possibly due to motional flexibility. Based on the resultant structure and the results of structure‐activity relationships, we propose the interaction sites of insulin‐like growth factor II with the type 2 insulin‐like growth factor receptor and the insulin‐like growth factor binding proteins. These sites partially overlap with each other at the opposite side of the putative binding surface to the insulin receptor and the type 1 insulin‐like growth factor receptor. We also discuss the interaction modes of insulin‐like growth factor II with the insulin receptor and the type 1 insulin‐like growth factor receptor.