4ELJ: Crystal Structure Of The Inactive Retinoblastoma Protein Phosphorylated At T373

Cyclin-dependent kinase (Cdk) phosphorylation of the Retinoblastoma protein (Rb) drives cell proliferation through inhibition of Rb complexes with E2F transcription factors and other regulatory proteins. We present the first structures of phosphorylated Rb that reveal the mechanism of its inactivation. S608 phosphorylation orders a flexible "pocket" domain loop such that it mimics and directly blocks E2F transactivation domain (E2F(TD)) binding. T373 phosphorylation induces a global conformational change that associates the pocket and N-terminal domains (RbN). This first multidomain Rb structure demonstrates a novel role for RbN in allosterically inhibiting the E2F(TD)-pocket association and protein binding to the pocket "LxCxE" site. Together, these structures detail the regulatory mechanism for a canonical growth-repressive complex and provide a novel example of how multisite Cdk phosphorylation induces diverse structural changes to influence cell cycle signaling.
PDB ID: 4ELJDownload
MMDB ID: 99949
PDB Deposition Date: 2012/4/10
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 4ELJ: monomeric; determined by author and by software (PISA)
Molecular Components in 4ELJ
Label Count Molecule
Protein (1 molecule)
Retinoblastoma-associated Protein(Gene symbol: RB1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB