1eaz: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 1eaz |SIZE=350|CAPTION= <scene name='initialview01'>1eaz</scene>, resolution 1.4Å | |PDB= 1eaz |SIZE=350|CAPTION= <scene name='initialview01'>1eaz</scene>, resolution 1.4Å | ||
|SITE= <scene name='pdbsite=LBS:Lbs+Stands+For+Lipid+Binding+Site.+Cb+Atom+Responsible+F+...'>LBS</scene> | |SITE= <scene name='pdbsite=LBS:Lbs+Stands+For+Lipid+Binding+Site.+Cb+Atom+Responsible+F+...'>LBS</scene> | ||
|LIGAND= <scene name='pdbligand=CIT:CITRIC ACID'>CIT</scene> | |LIGAND= <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1eaz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eaz OCA], [http://www.ebi.ac.uk/pdbsum/1eaz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1eaz RCSB]</span> | |||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==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). | 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== | ==About this Structure== | ||
| Line 30: | Line 30: | ||
[[Category: Dowler, S.]] | [[Category: Dowler, S.]] | ||
[[Category: Thomas, C C.]] | [[Category: Thomas, C C.]] | ||
[[Category: 4)-bisphosphate]] | [[Category: 4)-bisphosphate]] | ||
[[Category: ph domain]] | [[Category: ph domain]] | ||
| Line 36: | Line 35: | ||
[[Category: signalling]] | [[Category: signalling]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:59:01 2008'' | ||
