Do All X-ray Structures of Protein-Ligand Complexes Represent Functional States? EPOR, a Case Study.

ABSTRACT: Based on differences between the x-ray crystal structures of ligand-bound and unbound forms, the activation of the erythropoietin receptor (EPOR) was initially proposed to involve a cross-action scissorlike motion. However, the validity of the motions involved in the scissorlike model has been recently challenged. Here, atomistic molecular dynamics simulations are used to examine the structure of the extracellular domain of the EPOR dimer in the presence and absence of erythropoietin and a series of agonistic or antagonistic mimetic peptides free in solution. The simulations suggest that in the absence of crystal packing effects, the EPOR chains in the different dimers adopt very similar conformations with no clear distinction between the agonist and antagonist-bound complexes. This questi

SUBMITTER: Corbett MSP 

PROVIDER: S-EPMC5340159 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature