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| ==A PH domain within OCRL bridges clathrin mediated membrane trafficking to phosphoinositide metabolism== | | ==A PH domain within OCRL bridges clathrin mediated membrane trafficking to phosphoinositide metabolism== |
- | <StructureSection load='2kig' size='340' side='right' caption='[[2kig]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kig' size='340' side='right'caption='[[2kig]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[2kig]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KIG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kig]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KIG FirstGlance]. <br> |
- | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Inpp5b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Inpp5b ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> |
- | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2kig FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kig OCA], [http://pdbe.org/2kig PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kig RCSB], [http://www.ebi.ac.uk/pdbsum/2kig PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kig ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kig FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kig OCA], [https://pdbe.org/2kig PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kig RCSB], [https://www.ebi.ac.uk/pdbsum/2kig PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kig ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/I5P2_MOUSE I5P2_MOUSE]] Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events.<ref>PMID:11311145</ref> <ref>PMID:9525932</ref> | + | [[https://www.uniprot.org/uniprot/I5P2_MOUSE I5P2_MOUSE]] Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events.<ref>PMID:11311145</ref> <ref>PMID:9525932</ref> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| + | [[Category: Large Structures]] |
| [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| [[Category: Camilli, P De]] | | [[Category: Camilli, P De]] |
| Structural highlights
Function
[I5P2_MOUSE] Hydrolyzes phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P2) and the signaling molecule phosphatidylinositol 1,4,5-trisphosphate (PtIns(1,4,5)P3), and thereby modulates cellular signaling events.[1] [2]
Publication Abstract from PubMed
OCRL, whose mutations are responsible for Lowe syndrome and Dent disease, and INPP5B are two similar proteins comprising a central inositol 5-phosphatase domain followed by an ASH and a RhoGAP-like domain. Their divergent NH2-terminal portions remain uncharacterized. We show that the NH2-terminal region of OCRL, but not of INPP5B, binds clathrin heavy chain. OCRL, which in contrast to INPP5B visits late stage endocytic clathrin-coated pits, was earlier shown to contain another binding site for clathrin in its COOH-terminal region. NMR structure determination further reveals that despite their primary sequence dissimilarity, the NH2-terminal portions of both OCRL and INPP5B contain a PH domain. The novel clathrin-binding site in OCRL maps to an unusual clathrin-box motif located in a loop of the PH domain, whose mutations reduce recruitment efficiency of OCRL to coated pits. These findings suggest an evolutionary pressure for a specialized function of OCRL in bridging phosphoinositide metabolism to clathrin-dependent membrane trafficking.
A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism.,Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P EMBO J. 2009 Jul 8;28(13):1831-42. Epub 2009 Jun 18. PMID:19536138[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ O'Malley CJ, McColl BK, Kong AM, Ellis SL, Wijayaratnam AP, Sambrook J, Mitchell CA. Mammalian inositol polyphosphate 5-phosphatase II can compensate for the absence of all three yeast Sac1-like-domain-containing 5-phosphatases. Biochem J. 2001 May 1;355(Pt 3):805-17. PMID:11311145
- ↑ Matzaris M, O'Malley CJ, Badger A, Speed CJ, Bird PI, Mitchell CA. Distinct membrane and cytosolic forms of inositol polyphosphate 5-phosphatase II. Efficient membrane localization requires two discrete domains. J Biol Chem. 1998 Apr 3;273(14):8256-67. PMID:9525932
- ↑ Mao Y, Balkin DM, Zoncu R, Erdmann KS, Tomasini L, Hu F, Jin MM, Hodsdon ME, De Camilli P. A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism. EMBO J. 2009 Jul 8;28(13):1831-42. Epub 2009 Jun 18. PMID:19536138 doi:10.1038/emboj.2009.155
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