Solution structure of human insulin-like growth factor II; recognition sites for receptors and binding proteins.
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.
Terasawa
H
H
Department of Molecular Physiology, Tokyo Metropolitan Institute of Medical Science.
Kohda
D
D
Hatanaka
H
H
Nagata
K
K
Higashihashi
N
N
Fujiwara
H
H
Sakano
K
K
Inagaki
F
F
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D016415:Sequence Alignment; D012996:Solutions
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D017527:Receptor, IGF Type 2; D012996:Solutions; D007335:Insulin-Like Growth Factor II