Title : The first three
domains of the
insulin receptor differ structurally from the
insulin-like growth factor
1 receptor in the
regions governing ligand specificity
Abstract :
- The insulin receptor ( IR ) and the type- 1 insulin-like growth factor receptor ( IGF1R ) are homologous multidomain proteins that bind insulin and IGF with differing specificity
- Here we report the crystal structure of the first three domains (L 1-CR-L2) of human IR at 2.3 A resolution and compare it with the previously determined structure of the corresponding fragment of IGF1R
- The most important differences seen between the two receptors are in the two regions governing ligand specificity
- The first is at the corner of the ligand-binding surface of the L 1 domain , where the side chain of F39 in IR forms part of the ligand binding surface involving the second (central) beta-sheet
- This is very different to the location of its counterpart in IGF1R , S35, which is not involved in ligand binding
- The second major difference is in the sixth module of the CR domain , where IR contains a larger loop that protrudes further into the ligand-binding pocket
- This module, which governs IGF1-binding specificity, shows negligible sequence identity, significantly more alpha-helix, an additional disulfide bond, and opposite electrostatic potential compared to that of the IGF1R
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
- 0. insulin receptor, domains
- 0. insulin-like growth factor 1 receptor, regions
- 2. IGF1R, fragment
- 2. IR, domains
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):