Engineering synthetic antibody binders for allosteric inhibition of prolactin receptor signaling.

ABSTRACT:

Background

Many receptors function by binding to multiple ligands, each eliciting a distinct biological output. The extracellular domain of the human prolactin receptor (hPRL-R) uses an identical epitope to bind to both prolactin (hPRL) and growth hormone (hGH), yet little is known about how each hormone binding event triggers the appropriate response.

Findings

Here, we utilized a phage display library to generate synthetic antibodies (sABs) that preferentially modulate hPRL-R function in a hormone-dependent fashion. We determined the crystal structure of a sAB-hPRL-R complex, which revealed a novel allosteric mechanism of antagonism, whereby the sAB traps the receptor in a conformation more suitable for hGH binding than hPRL. This was validated by examining the effect of th

SUBMITTER: Rizk SS 

PROVIDER: S-EPMC4300558 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature