Incorporating an allosteric regulatory site in an antibody through backbone design.

ABSTRACT: Allosteric regulation underlies living cells' ability to sense changes in nutrient and signaling-molecule concentrations, but the ability to computationally design allosteric regulation into non-allosteric proteins has been elusive. Allosteric-site design is complicated by the requirement to encode the relative stabilities of active and inactive conformations of the same protein in the presence and absence of both ligand and effector. To address this challenge, we used Rosetta to design the backbone of the flexible heavy-chain complementarity-determining region 3 (HCDR3), and used geometric matching and sequence optimization to place a Zn²⁺ -coordination site in a fluorescein-binding antibody. We predicted that due to HCDR3's flexibility, the fluorescein-binding pocket would con

SUBMITTER: Khersonsky O 

PROVIDER: S-EPMC5368060 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature