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'''CRYSTAL STRUCTURE OF THE PHOSPHOINOSITOL (3,4)-BISPHOSPHATE BINDING PH DOMAIN OF TAPP1 FROM HUMAN.''' | '''CRYSTAL STRUCTURE OF THE PHOSPHOINOSITOL (3,4)-BISPHOSPHATE BINDING PH DOMAIN OF TAPP1 FROM HUMAN.''' | ||
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[[Category: Dowler, S.]] | [[Category: Dowler, S.]] | ||
[[Category: Thomas, C C.]] | [[Category: Thomas, C C.]] | ||
[[Category: | [[Category: Ph domain]] | ||
[[Category: Signalling]] | |||
[[Category: | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:53:15 2008'' | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 11:53, 2 May 2008
CRYSTAL STRUCTURE OF THE PHOSPHOINOSITOL (3,4)-BISPHOSPHATE BINDING PH DOMAIN OF TAPP1 FROM HUMAN.
Overview
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).
About this Structure
1EAZ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin homology (PH) domain of tandem PH-domain-containing protein 1 (TAPP1): molecular basis of lipid specificity., Thomas CC, Dowler S, Deak M, Alessi DR, van Aalten DM, Biochem J. 2001 Sep 1;358(Pt 2):287-94. PMID:11513726 Page seeded by OCA on Fri May 2 14:53:15 2008
