 PX Domain | |
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| Class:Phospholipid binding | |
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Structure:
 The structural basis for PX domain interactions with phosphoinositides have been determined from the structures of the PX domains of p40phox and Vmp7p in a complex with PI(3)P. Interactions between all PX domains and their bound phosphoinositides involve the 1-phosphate and the inositol ring. A hydrogen bond between a well-conserved residue, K92 (in p40phox), and the 1-phosphate is the most important interaction with this group. Y59 (in p40phox) forms the floor of the lipid-binding pocket in the PX domain, allowing the inositol ring of PI(3)P to stack tightly against it. This carbohydrate-aromatic stacking is likely to be a common feature of binding, since all PX domains have either Y or F at the analogous position.
Structure Reference:
Bravo, J. et al. (2001) Mol. Cell. 8(4): 829-839. PDB: 1H6H.
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Domain binding and function:
The Phox homology (PX) domain is a phospholipid-binding domain consisting of ~120 amino acids. The PX domain is found in more than 250 proteins, including the p40phox and p47phox components of the NADPH oxidase complex, sorting nexins, phospholipases D1 and 2 and the kinases PI3K and CISK. PX domains show an N-terminal three-stranded β-sheet, followed by a helical subdomain made up of four α-helices. PX domains preferentially bind to PtdIns(3)P, although some have been reported to bind other phosphoinositides. Proteins containing PX domains have been implicated in a wide spectrum of functions, including protein sorting, vesicular trafficking and phospholipids metabolism.
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Examples of Proteins:
| PX Domain Proteins |
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Binding Partners |
| p40phox |  |
PI(3)P |
| p47phox | |
PI(3,4)P2, PI(3)P |
| Vmp7 | |
PI(3)P |
SNX
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PI(3,5)P2, PI(4)P, PI(5)P
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PLD1
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PI(3,4,5)P3
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CISK
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PI(3,4,5)P3
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PI3K (Class II)
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PI(4,5)P2
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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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