Aromatic anchor at an invariant hormone-receptor interface: function of insulin residue B24 with application to protein design.

ABSTRACT: Crystallographic studies of insulin bound to fragments of the insulin receptor have recently defined the topography of the primary hormone-receptor interface. Here, we have investigated the role of Phe(B24), an invariant aromatic anchor at this interface and site of a human mutation causing diabetes mellitus. An extensive set of B24 substitutions has been constructed and tested for effects on receptor binding. Although aromaticity has long been considered a key requirement at this position, Met(B24) was found to confer essentially native affinity and bioactivity. Molecular modeling suggests that this linear side chain can serve as an alternative hydrophobic anchor at the hormone-receptor interface. These findings motivated further substitution of Phe(B24) by cyclohexanylalanine (Cha), whic

SUBMITTER: Pandyarajan V 

PROVIDER: S-EPMC4263875 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature