pRB and the LXCXE motif. (A) A repressor complex composed of an E2F transcription factor, pRB, and a chromatin regulator is shown in G1. The interaction between pRB and the chromatin regulator is mediated by the peptide sequence LXCXE on the chromatin remodeling factor and the LXCXE binding cleft on pRB. Viral proteins like TAg, E7, and E1A can disrupt this complex because they contain an LXCXE motif. Disruption of this pRB-containing complex can advance the cell cycle into S-phase. (B) The LXCXE binding cleft on pRB is a shallow groove formed between two parallel helices. The amino acid sequence of these helices in human pRB is aligned to the analogous sequences from pRB-family proteins from humans, corn, fruit flies, worms, and algae. Shaded amino acids are identical between all protein comparisons. The asterisk denotes amino acids whose side chains make direct contact with LXCXE in the crystal structure reported by Lee et al. .