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| ==X-Ray structure of human PEX3 in complex with a PEX19 derived peptide== | | ==X-Ray structure of human PEX3 in complex with a PEX19 derived peptide== |
| <StructureSection load='3mk4' size='340' side='right' caption='[[3mk4]], [[Resolution|resolution]] 2.42Å' scene=''> | | <StructureSection load='3mk4' size='340' side='right'caption='[[3mk4]], [[Resolution|resolution]] 2.42Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3mk4]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MK4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MK4 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3mk4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MK4 FirstGlance]. <br> |
| </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PEX3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.42Å</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=3mk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mk4 OCA], [http://pdbe.org/3mk4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mk4 RCSB], [http://www.ebi.ac.uk/pdbsum/3mk4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mk4 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=3mk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mk4 OCA], [https://pdbe.org/3mk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mk4 RCSB], [https://www.ebi.ac.uk/pdbsum/3mk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mk4 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease == | | == Disease == |
| [[http://www.uniprot.org/uniprot/PEX3_HUMAN PEX3_HUMAN]] Defects in PEX3 are the cause of peroxisome biogenesis disorder complementation group 12 (PBD-CG12) [MIM:[http://omim.org/entry/614882 614882]]; also known as PBD-CGG. PBD refers to a group of peroxisomal disorders arising from a failure of protein import into the peroxisomal membrane or matrix. The PBD group is comprised of four disorders: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum. The PBD group is genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies.<ref>PMID:10958759</ref> Defects in PEX3 are a cause of peroxisome biogenesis disorder 10A (PBD10A) [MIM:[http://omim.org/entry/614882 614882]]. A fatal peroxisome biogenesis disorder characterized by dysmorphic facial features, hepatomegaly, ocular abnormalities, renal cysts, hearing impairment, profound psychomotor retardation, severe hypotonia and neonatal seizures. Death occurs within the first year of life.<ref>PMID:10848631</ref> <ref>PMID:10958759</ref> [[http://www.uniprot.org/uniprot/PEX19_HUMAN PEX19_HUMAN]] Defects in PEX19 are the cause of peroxisome biogenesis disorder complementation group 14 (PBD-CG14) [MIM:[http://omim.org/entry/614886 614886]]; also known as PBD-CGJ. PBD refers to a group of peroxisomal disorders arising from a failure of protein import into the peroxisomal membrane or matrix. The PBD group is comprised of four disorders: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum. The PBD group is genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies.<ref>PMID:20683989</ref> Defects in PEX19 are the cause of peroxisome biogenesis disorder 12A (PBD12A) [MIM:[http://omim.org/entry/614886 614886]]. A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life. | | [https://www.uniprot.org/uniprot/PEX3_HUMAN PEX3_HUMAN] Defects in PEX3 are the cause of peroxisome biogenesis disorder complementation group 12 (PBD-CG12) [MIM:[https://omim.org/entry/614882 614882]; also known as PBD-CGG. PBD refers to a group of peroxisomal disorders arising from a failure of protein import into the peroxisomal membrane or matrix. The PBD group is comprised of four disorders: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum. The PBD group is genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies.<ref>PMID:10958759</ref> Defects in PEX3 are a cause of peroxisome biogenesis disorder 10A (PBD10A) [MIM:[https://omim.org/entry/614882 614882]. A fatal peroxisome biogenesis disorder characterized by dysmorphic facial features, hepatomegaly, ocular abnormalities, renal cysts, hearing impairment, profound psychomotor retardation, severe hypotonia and neonatal seizures. Death occurs within the first year of life.<ref>PMID:10848631</ref> <ref>PMID:10958759</ref> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/PEX3_HUMAN PEX3_HUMAN]] Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes.<ref>PMID:10848631</ref> <ref>PMID:15007061</ref> [[http://www.uniprot.org/uniprot/PEX19_HUMAN PEX19_HUMAN]] Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cytoplasm by interacting with their hydrophobic membrane-spanning domains, and targets them to the peroxisome membrane by binding to the integral membrane protein PEX3. Excludes CDKN2A from the nucleus and prevents its interaction with MDM2, which results in active degradation of TP53.<ref>PMID:10051604</ref> <ref>PMID:10704444</ref> <ref>PMID:11259404</ref> <ref>PMID:11883941</ref> <ref>PMID:15007061</ref> <ref>PMID:14709540</ref> | | [https://www.uniprot.org/uniprot/PEX3_HUMAN PEX3_HUMAN] Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes.<ref>PMID:10848631</ref> <ref>PMID:15007061</ref> |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3mk4 ConSurf]. | | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3mk4 ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The human peroxins PEX3 and PEX19 play a central role in peroxisomal membrane biogenesis. The membrane-anchored PEX3 serves as the receptor for cytosolic PEX19, which in turn recognizes newly synthesized peroxisomal membrane proteins. After delivering these proteins to the peroxisomal membrane, PEX19 is recycled to the cytosol. The molecular mechanisms underlying these processes are not well understood. Here, we report the crystal structure of the cytosolic domain of PEX3 in complex with a PEX19-derived peptide. PEX3 adopts a novel fold that is best described as a large helical bundle. A hydrophobic groove at the membrane-distal end of PEX3 engages the PEX19 peptide with nanomolar affinity. Mutagenesis experiments identify phenylalanine 29 in PEX19 as critical for this interaction. Because key PEX3 residues involved in complex formation are highly conserved across species, the observed binding mechanism is of general biological relevance.
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| Insights into peroxisome function from the structure of PEX3 in complex with a soluble fragment of PEX19.,Schmidt F, Treiber N, Zocher G, Bjelic S, Steinmetz MO, Kalbacher H, Stehle T, Dodt G J Biol Chem. 2010 Aug 13;285(33):25410-7. Epub 2010 Jun 16. PMID:20554521<ref>PMID:20554521</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 3mk4" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Dodt, G]] | | [[Category: Large Structures]] |
| [[Category: Schmidt, F]] | | [[Category: Dodt G]] |
| [[Category: Stehle, T]] | | [[Category: Schmidt F]] |
| [[Category: Treiber, N]] | | [[Category: Stehle T]] |
| [[Category: Membrane]]
| | [[Category: Treiber N]] |
| [[Category: Peroxisome]]
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| [[Category: Protein transport]]
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