1eaz: Difference between revisions

Phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] and its, immediate breakdown product PtdIns(3,4)P(2) function as second messengers, in growth factor- and insulin-induced signalling pathways. One of the ways, that these 3-phosphoinositides are known to regulate downstream signalling, events is by attracting proteins that possess specific PtdIns-binding, pleckstrin homology (PH) domains to the plasma membrane. Many of these, proteins, such as protein kinase B, phosphoinositide-dependent kinase 1, and the dual adaptor for phosphotyrosine and 3-phosphoinositides (DAPP1), interact with both PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2) with similar, affinity. Recently, a new PH-domain-containing protein, termed tandem, PH-domain-containing protein (TAPP) 1, was described which is the first, protein reported to bind PtdIns(3,4)P(2) specifically. Here we describe, the crystal structure of the PtdIns(3,4)P(2)-binding PH domain of TAPP1 at, 1.4 A (1 A=0.1 nm) resolution in complex with an ordered citrate molecule., The structure is similar to the known structure of the PH domain of DAPP1, around the D-3 and D-4 inositol-phosphate-binding sites. However, a, glycine residue adjacent to the D-5 inositol-phosphate-binding site in, DAPP1 is substituted for a larger alanine residue in TAPP1, which also, induces a conformational change in the neighbouring residues. We show that, mutation of this glycine to alanine in DAPP1 converts DAPP1 into a, TAPP1-like PH domain that only interacts with PtdIns(3,4)P(2), whereas the, alanine to glycine mutation in TAPP1 permits the TAPP1 PH domain to, interact with PtdIns(3,4,5)P(3).

1EAZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CIT as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: LBS. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EAZ OCA].  

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