Mapping the homodimer interface of an optimized, artificial, transmembrane protein activator of the human erythropoietin receptor.

ABSTRACT: Transmembrane proteins constitute a large fraction of cellular proteins, and specific interactions involving membrane-spanning protein segments play an important role in protein oligomerization, folding, and function. We previously isolated an artificial, dimeric, 44-amino acid transmembrane protein that activates the human erythropoietin receptor (hEPOR) in trans. This artificial protein supports limited erythroid differentiation of primary human hematopoietic progenitor cells in vitro, even though it does not resemble erythropoietin, the natural ligand of this receptor. Here, we used a directed-evolution approach to explore the structural basis for the ability of transmembrane proteins to activate the hEPOR. A library that expresses thousands of mutants of the transmembrane activator was

SUBMITTER: Cohen EB 

PROVIDER: S-EPMC4005772 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature