1FHW: Structure Of The Pleckstrin Homology Domain From Grp1 In Complex With Inositol(1,3,4,5,6)pentakisphosphate

Pleckstrin homology (PH) domains are protein modules of around 120 amino acids found in many proteins involved in cellular signaling. Certain PH domains drive signal-dependent membrane recruitment of their host proteins by binding strongly and specifically to lipid second messengers produced by agonist-stimulated phosphoinositide 3-kinases (PI 3-Ks). We describe X-ray crystal structures of two different PH domains bound to Ins(1,3,4,5)P4, the head group of the major PI 3-K product PtdIns(3,4,5)P3. One of these PH domains (from Grp1) is PtdIns(3,4,5)P3 specific, while the other (from DAPP1/PHISH) binds strongly to both PtdIns(3,4,5)P3 and its 5'-dephosphorylation product, PtdIns(3,4)P2. Comparison of the two structures provides an explanation for the distinct phosphoinositide specificities of the two PH domains and allows us to predict the 3-phosphoinositide selectivity of uncharacterized PH domains.
PDB ID: 1FHWDownload
MMDB ID: 14111
PDB Deposition Date: 2000/8/2
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Similar Structures:
Biological Unit for 1FHW: monomeric; determined by author
Molecular Components in 1FHW
Label Count Molecule
Protein (1 molecule)
Guanine Nucleotide Exchange Factor and Integrin Binding Protein Homolog Grp1(Gene symbol: Cyth3)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB