The possible mechanism of binding interaction of insulin molecule with its receptor.
Detailed structural comparisons and investigation of DPI, 2 Zn insulin and some other derivatives of insulin were performed by the least-squares superimposition technique and the graphics technique. It is pointed out in this paper that the binding interaction with the receptor molecule should take place mainly on an amphipathic surface of the insulin molecule. In the middle, there is a hydrophobic surface with an area of about 150 A2 consisting of many hydrophobic residues; while the polar or charged groups distributing around the hydrophobic surface construct a hydrophilic zone. The hydrophobic surface is usually covered by the extended B-chain C-terminal peptides with great mobility and protected from the solvent molecules. The angle between the amphipathic surface and the surface of dimerization is about 20 degrees. The results from the detailed structural comparison between Al-(L-Trp) insulin and Al-(D-Trp) insulin have provided a very good explanation to their great difference in biological activity, and confirmed our proposed binding interaction model of the insulin molecule with its receptor as well.
Liang
D C
DC
Institute of Biophysics, Academia Sinica, Beijing, PRC.
Chang
W R
WR
Zhang
J P
JP
Wan
Z L
ZL
D000818:Animals; D001665:Binding Sites; D007328:Insulin / Q000031:analogs & derivatives / Q000737:chemistry*; D008968:Molecular Conformation; D011972:Receptor, Insulin / Q000737:chemistry*; D013552:Swine
D007328:Insulin; C007285:insulin, despentapeptide(B26-B30)-; D011972:Receptor, Insulin