Phospholipid Binding: PH Domain

The PH domain from rat PLC δ1 bound to Ins(1,4,5)P3 (red).

Domain Binding and Function

Pleckstrin-homology (PH) domains are structurally well-characterized modules of ~120 amino acids found in a wide variety of signaling proteins involved intracellular trafficking, cellular signaling and cytoskeletal remodeling. The human proteome contains some 250 PH domains, all of which share a common core fold consisting of a 7-stranded β-sandwich formed from two near-orthogonal β-sheets. The basic residues in the β1/β2 loop of the PH domain form a well-defined binding site with the phosphates of phosphoionositide headgroups. Some PH domains bind with high affinity (low µM or nM Kd) to specific phosphoinositides such as phosphatidylinositol- 4,5-bisphosphate, PI-3, 4-P2 or PI-3,4,5-P3. Binding to phosphoinositides may allow PH proteins to respond to lipid messengers by localizing to membranes and transmitting signals to downstream targets.

Structure Reference

  1. Ferguson, K.M. et al. (1995) Cell 83(6), 1037–1046.

Examples of Domain Proteins

Phospholipid Binding: PH Domain

Binding Examples

PH Domain Proteins Specific Phosphoinositide Ligand
Phospholipase C-δ; mSos1, RasGAP; Tsk, pleckstrin PI-(4,5)-P2
Btk; Grp1 PI-(3,4,5)-P3
Akt; DAPP1; TAPP1 PI-(3,4)-P2