1FHW

Structure of the pleckstrin homology domain from GRP1 in complex with inositol(1,3,4,5,6)pentakisphosphate

Summary for 1FHW

• Entry DOI: 10.2210/pdb1fhw/pdb
• Related: 1FHX
• Descriptor: GUANINE NUCLEOTIDE EXCHANGE FACTOR AND INTEGRIN BINDING PROTEIN HOMOLOG GRP1, INOSITOL-(1,3,4,5,6)-PENTAKISPHOSPHATE, SULFATE ION, ... (4 entities in total)
• Functional Keywords: pleckstrin, 3-phosphoinositides, inositol tetrakisphosphate signal transduction protein, guanine nucleotide exchange factor, signaling protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 31694.99

Authors

Ferguson, K.M.,Kavran, J.M.,Sankaran, V.G.,Fournier, E.,Isakoff, S.J.,Skolnik, E.Y.,Lemmon, M.A. (deposition date: 2000-08-02, release date: 2000-08-23, Last modification date: 2024-11-13)

Primary citation

Ferguson, K.M.,Kavran, J.M.,Sankaran, V.G.,Fournier, E.,Isakoff, S.J.,Skolnik, E.Y.,Lemmon, M.A.
Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains
Mol.Cell, 6:373-384, 2000

PubMed Abstract: 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.

PubMed: 10983984
DOI: 10.1016/S1097-2765(00)00037-X

Experimental method

X-RAY DIFFRACTION (1.9 Å)