DOC_CyclinA_RxL_1

Cyclin docking motif

Substrate recognition site that interacts with cyclin and thereby increases phosphorylation by cyclin/Cdk complexes. Predicted proteins should have a Cdk phosphorylation site. Also used by cyclin/Cdk inhibitors.

The classical cyclin docking motif pattern is mainly derived from peptides bound to Cyclin A, for which there are several structures in complex with the peptide. Although the motif is often called RxL, there are actually four core binding residues, with only the Leucine being fully conserved. The motif binds in a hydrophobic groove with charged residues lining the edge. Peptide backbone hydrogen bonds guide the four core binding residues into the groove. Preceding the core motif, there is a clear but non-essential preference for basic residues. After the core, there is a clear but flexible preference for acidic residues. The first core binding position is quite shallow, accepting either hydrophobic or basic residues. It is followed by a residue facing outwards which cannot accept the short acidic residue Asp. The next residue lies in a pocket and must be either Arg or Lys. It is followed by a residue facing outwards which cannot accept the short acidic residue Asp. Then comes the Leu residue fitting into the hydrophobic groove. Flexible spacing then allows one optional externally facing residue. The final core hydrophobic residue is one of Phe, Pro, Leu or Met. The derived regular expression pattern captures the core motif and approximates the weaker charge preference to either side.

Cyclin_N (PF00134) Cyclin, N-terminal domain (Stochiometry: 1 : 1)

PDB Structure: 1H24