Crystal structure of the unliganded retinoblastoma protein pocket domain.

The retinoblastoma protein (Rb) regulates cell proliferation through its association with E2F transcription factors and other proteins. The Rb “pocket” domain primarily facilitates protein-protein interactions, and several structures of the pocket bound to E2F and tumorigenic viral proteins have been reported. We report here the first crystal structure of the pocket domain without bound ligand. We find that ligand association results in observable structural changes at the binding sites but no significant changes to the overall conformation of the domain. These data support models for regulation of Rb-E2F binding that do not require considerable structural changes in the pocket domain.