2qv2: Difference between revisions
New page: left|200px<br /> <applet load="2qv2" size="450" color="white" frame="true" align="right" spinBox="true" caption="2qv2, resolution 2.40Å" /> '''A role of the Lowe ... |
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[[Image:2qv2.gif|left|200px]]<br /> | [[Image:2qv2.gif|left|200px]]<br /><applet load="2qv2" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2qv2, resolution 2.40Å" /> | caption="2qv2, resolution 2.40Å" /> | ||
'''A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway'''<br /> | '''A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway'''<br /> | ||
== | ==Overview== | ||
Mutations in the inositol 5-phosphatase OCRL are responsible for Lowe, syndrome, whose manifestations include mental retardation and renal, Fanconi syndrome. OCRL has been implicated in membrane trafficking, but, disease mechanisms remain unclear. We show that OCRL visits late-stage, endocytic clathrin-coated pits and binds the Rab5 effector APPL1 on, peripheral early endosomes. The interaction with APPL1, which is mediated, by the ASH-RhoGAP-like domains of OCRL and is abolished by disease, mutations, provides a link to protein networks implicated in the, reabsorptive function of the kidney and in the trafficking and signaling, of growth factor receptors in the brain. Crystallographic studies reveal a, role of the ASH-RhoGAP-like domains in positioning the phosphatase domain, at the membrane interface and a clathrin box protruding from the, RhoGAP-like domain. Our results support a role of OCRL in the early, endocytic pathway, consistent with the predominant localization of its, preferred substrates, PI(4,5)P(2) and PI(3,4,5)P(3), at the cell surface. | |||
==About this Structure== | ==About this Structure== | ||
2QV2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Phosphoinositide_5-phosphatase Phosphoinositide 5-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.36 3.1.3.36] Full crystallographic information is available from [http:// | 2QV2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Phosphoinositide_5-phosphatase Phosphoinositide 5-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.36 3.1.3.36] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QV2 OCA]. | ||
==Reference== | |||
A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway., Erdmann KS, Mao Y, McCrea HJ, Zoncu R, Lee S, Paradise S, Modregger J, Biemesderfer D, Toomre D, De Camilli P, Dev Cell. 2007 Sep;13(3):377-90. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17765681 17765681] | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Phosphoinositide 5-phosphatase]] | [[Category: Phosphoinositide 5-phosphatase]] | ||
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[[Category: rhogap]] | [[Category: rhogap]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:06:49 2008'' | ||
Revision as of 13:06, 23 January 2008
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A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway
OverviewOverview
Mutations in the inositol 5-phosphatase OCRL are responsible for Lowe, syndrome, whose manifestations include mental retardation and renal, Fanconi syndrome. OCRL has been implicated in membrane trafficking, but, disease mechanisms remain unclear. We show that OCRL visits late-stage, endocytic clathrin-coated pits and binds the Rab5 effector APPL1 on, peripheral early endosomes. The interaction with APPL1, which is mediated, by the ASH-RhoGAP-like domains of OCRL and is abolished by disease, mutations, provides a link to protein networks implicated in the, reabsorptive function of the kidney and in the trafficking and signaling, of growth factor receptors in the brain. Crystallographic studies reveal a, role of the ASH-RhoGAP-like domains in positioning the phosphatase domain, at the membrane interface and a clathrin box protruding from the, RhoGAP-like domain. Our results support a role of OCRL in the early, endocytic pathway, consistent with the predominant localization of its, preferred substrates, PI(4,5)P(2) and PI(3,4,5)P(3), at the cell surface.
About this StructureAbout this Structure
2QV2 is a Single protein structure of sequence from Homo sapiens. Active as Phosphoinositide 5-phosphatase, with EC number 3.1.3.36 Full crystallographic information is available from OCA.
ReferenceReference
A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway., Erdmann KS, Mao Y, McCrea HJ, Zoncu R, Lee S, Paradise S, Modregger J, Biemesderfer D, Toomre D, De Camilli P, Dev Cell. 2007 Sep;13(3):377-90. PMID:17765681
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