LIG_CtBP_PxDLS_1

CtBP ligand motif

The PxDLS motif is present in a number of nuclear proteins, including certain transcription factors and HDACs, that recruit CtBP (C-terminal binding protein) into nuclear complexes. CtBP has a generally repressive effect on transcription and must be removed to active CtBP regulated genes.

The PxDLS motif pattern is based on the conservation of reported sequence instances together with the structure of the CtBP domain in complex with a PxDLS peptide (1HL3). Beta-augmentation at the sheet edge places the peptide sidechains in specific places on the CtBP surface. Pro at position 1 makes an H-bond to strand edge backbone and fits in a hydrophobic pocket that will not accommodate other residues (Gly with no side chain may be the least disruptive). Position 2 contributes to beta augmentation so that the semi-conserved sidechain is placed in a shallow hydrophobic pocket, which also allows Glu due to proximity of surface positive charge. Position 3 is most often Asp, probably due to favourable charged residue proximity but is surface accessible and accepts some changes. Position 4 contributes to beta augmentation so that the sidechain enters a deep hydrophobic groove that fits to Leu and would probably allow Met but reject most other residues. Position 5 has a Ser-Thr preference but appears to accept R (as in HDACs) and some other mostly small residues. Following the core peptide there are clear preferences for Lys or Arg but these are not a strict requirement. However the conserved GLDLSKK motif in Hic1 is reported to bind CtBP but lacks Pro: Therefore for Gly at position 1 which must weaken the interaction, the motif in ELM requires C-terminal positive charge compensation.

2-Hacid_dh (PF00389) D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain (Stochiometry: 1 : 1)