3qbt

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{{STRUCTURE_3qbt| PDB=3qbt | SCENE= }}
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==Crystal structure of OCRL1 540-678 in complex with Rab8a:GppNHp==
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===Crystal structure of OCRL1 540-678 in complex with Rab8a:GppNHp===
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<StructureSection load='3qbt' size='340' side='right' caption='[[3qbt]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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{{ABSTRACT_PUBMED_21378754}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3qbt]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QBT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QBT FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MEL, RAB8, RAB8A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), INPP5F, OCRL, OCRL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
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<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=3qbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qbt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qbt RCSB], [http://www.ebi.ac.uk/pdbsum/3qbt PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/OCRL_HUMAN OCRL_HUMAN]] Defects in OCRL are the cause of Lowe oculocerebrorenal syndrome (OCRL) [MIM:[http://omim.org/entry/309000 309000]]. It is an X-linked multisystem disorder affecting eyes, nervous system, and kidney. It is characterized by hydrophthalmia, cataract, mental retardation, vitamin D-resistant rickets, aminoaciduria, and reduced ammonia production by the kidney. Ocular abnormalities include cataract, glaucoma, microphthalmos, and decreased visual acuity. Developmental delay, hypotonia, behavior abnormalities, and areflexia are also present. Renal tubular involvement is characterized by impaired reabsorption of bicarbonate, amino acids, and phosphate. Musculoskeletal abnormalities such as joint hypermobility, dislocated hips, and fractures may develop as consequences of renal tubular acidosis and hypophosphatemia. Cataract is the only significant manifestation in carriers and is detected by slit-lamp examination.<ref>PMID:20133602</ref> <ref>PMID:21233288</ref> <ref>PMID:9199559</ref> <ref>PMID:9682219</ref> <ref>PMID:9632163</ref> <ref>PMID:9788721</ref> <ref>PMID:10923037</ref> <ref>PMID:10767176</ref> <ref>PMID:19168822</ref> <ref>PMID:21031565</ref> Defects in OCRL are the cause of Dent disease type 2 (DD2) [MIM:[http://omim.org/entry/300555 300555]]. DD2 is a renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Characteristic abnormalities include low-molecular-weight proteinuria and other features of Fanconi syndrome, such as glycosuria, aminoaciduria, and phosphaturia, but typically do not include proximal renal tubular acidosis. Progressive renal failure is common, as are nephrocalcinosis and kidney stones.<ref>PMID:21031565</ref> <ref>PMID:15627218</ref> <ref>PMID:17384968</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/RAB8A_HUMAN RAB8A_HUMAN]] May be involved in vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B and RAB11A participates in epithelial cell polarization.<ref>PMID:20890297</ref> <ref>PMID:21282656</ref> [[http://www.uniprot.org/uniprot/OCRL_HUMAN OCRL_HUMAN]] Converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate. Also converts inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate and inositol 1,3,4,5-tetrakisphosphate to inositol 1,3,4-trisphosphate. May function in lysosomal membrane trafficking by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with lysosomes. Involved in primary cilia assembly.<ref>PMID:22543976</ref> <ref>PMID:22228094</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The oculocerebrorenal syndrome of Lowe (OCRL), also called Lowe syndrome, is characterized by defects of the nervous system, the eye and the kidney. Lowe syndrome is a monogenetic X-linked disease caused by mutations of the inositol-5-phosphatase OCRL1. OCRL1 is a membrane-bound protein recruited to membranes via interaction with a variety of Rab proteins. The structural and kinetic basis of OCRL1 for the recognition of several Rab proteins is unknown. In this study, we report the crystal structure of the Rab-binding domain (RBD) of OCRL1 in complex with Rab8a and the kinetic binding analysis of OCRL1 with several Rab GTPases (Rab1b, Rab5a, Rab6a and Rab8a). In contrast to other effectors that bind their respective Rab predominantly via alpha-helical structure elements, the Rab-binding interface of OCRL1 consists mainly of the IgG-like beta-strand structure of the ASPM-SPD-2-Hydin domain as well as one alpha-helix. Our results give a deeper structural understanding of disease-causing mutations of OCRL1 affecting Rab binding.
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==Disease==
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A structural basis for Lowe syndrome caused by mutations in the Rab-binding domain of OCRL1.,Hou X, Hagemann N, Schoebel S, Blankenfeldt W, Goody RS, Erdmann KS, Itzen A EMBO J. 2011 Mar 4. PMID:21378754<ref>PMID:21378754</ref>
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[[http://www.uniprot.org/uniprot/OCRL_HUMAN OCRL_HUMAN]] Defects in OCRL are the cause of Lowe oculocerebrorenal syndrome (OCRL) [MIM:[http://omim.org/entry/309000 309000]]. It is an X-linked multisystem disorder affecting eyes, nervous system, and kidney. It is characterized by hydrophthalmia, cataract, mental retardation, vitamin D-resistant rickets, aminoaciduria, and reduced ammonia production by the kidney. Ocular abnormalities include cataract, glaucoma, microphthalmos, and decreased visual acuity. Developmental delay, hypotonia, behavior abnormalities, and areflexia are also present. Renal tubular involvement is characterized by impaired reabsorption of bicarbonate, amino acids, and phosphate. Musculoskeletal abnormalities such as joint hypermobility, dislocated hips, and fractures may develop as consequences of renal tubular acidosis and hypophosphatemia. Cataract is the only significant manifestation in carriers and is detected by slit-lamp examination.<ref>PMID:20133602</ref><ref>PMID:21233288</ref><ref>PMID:9199559</ref><ref>PMID:9682219</ref><ref>PMID:9632163</ref><ref>PMID:9788721</ref><ref>PMID:10923037</ref><ref>PMID:10767176</ref><ref>PMID:19168822</ref><ref>PMID:21031565</ref> Defects in OCRL are the cause of Dent disease type 2 (DD2) [MIM:[http://omim.org/entry/300555 300555]]. DD2 is a renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. Characteristic abnormalities include low-molecular-weight proteinuria and other features of Fanconi syndrome, such as glycosuria, aminoaciduria, and phosphaturia, but typically do not include proximal renal tubular acidosis. Progressive renal failure is common, as are nephrocalcinosis and kidney stones.<ref>PMID:21031565</ref><ref>PMID:15627218</ref><ref>PMID:17384968</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/RAB8A_HUMAN RAB8A_HUMAN]] May be involved in vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B and RAB11A participates in epithelial cell polarization.<ref>PMID:20890297</ref><ref>PMID:21282656</ref> [[http://www.uniprot.org/uniprot/OCRL_HUMAN OCRL_HUMAN]] Converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 4-phosphate. Also converts inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate and inositol 1,3,4,5-tetrakisphosphate to inositol 1,3,4-trisphosphate. May function in lysosomal membrane trafficking by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with lysosomes. Involved in primary cilia assembly.<ref>PMID:22543976</ref><ref>PMID:22228094</ref>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[3qbt]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QBT OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:021378754</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Phosphoinositide 5-phosphatase]]
[[Category: Phosphoinositide 5-phosphatase]]
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[[Category: Blankenfeldt, W.]]
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[[Category: Blankenfeldt, W]]
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[[Category: Erdmann, K S.]]
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[[Category: Erdmann, K S]]
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[[Category: Goody, R S.]]
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[[Category: Goody, R S]]
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[[Category: Hagemann, N.]]
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[[Category: Hagemann, N]]
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[[Category: Hou, X.]]
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[[Category: Hou, X]]
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[[Category: Itzen, A.]]
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[[Category: Itzen, A]]
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[[Category: Schoebel, S.]]
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[[Category: Schoebel, S]]
[[Category: Appl1]]
[[Category: Appl1]]
[[Category: Ash]]
[[Category: Ash]]

Revision as of 07:44, 20 January 2015

Crystal structure of OCRL1 540-678 in complex with Rab8a:GppNHp

3qbt, resolution 2.00Å

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