3ajb

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{{STRUCTURE_3ajb| PDB=3ajb | SCENE= }}
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==Crystal Structure of human Pex3p in complex with N-terminal Pex19p peptide==
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===Crystal Structure of human Pex3p in complex with N-terminal Pex19p peptide===
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<StructureSection load='3ajb' size='340' side='right' caption='[[3ajb]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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{{ABSTRACT_PUBMED_21102411}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3ajb]] is a 2 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=3AJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3AJB FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hCG_18102, PEX3, TRG18 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), HK33, OK/SW-cl.22, PEX19, PXF ([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='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=3ajb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ajb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ajb RCSB], [http://www.ebi.ac.uk/pdbsum/3ajb PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/Q6FGP5_HUMAN Q6FGP5_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.
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== Function ==
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[[http://www.uniprot.org/uniprot/Q6FGP5_HUMAN Q6FGP5_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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Peroxisomes require peroxin (Pex) proteins for their biogenesis. The interaction between Pex3p, which resides on the peroxisomal membrane, and Pex19p, which resides in the cytosol, is crucial for peroxisome formation and the post-translational targeting of peroxisomal membrane proteins (PMPs). It is not known how Pex3p promotes the specific interaction with Pex19p for the purpose of PMP translocation. Here, we present the three-dimensional structure of the complex between a cytosolic domain of Pex3p and the binding-region peptide of Pex19p. The overall shape of Pex3p is a prolate spheroid with a novel fold, the 'twisted six-helix bundle.' The Pex19p-binding site is at an apex of the Pex3p spheroid. A 16-residue region of the Pex19p peptide forms an alpha-helix and makes a contact with Pex3p; this helix is disordered in the unbound state. The Pex19p peptide contains a characteristic motif, consisting of the leucine triad (Leu18, Leu21, Leu22), and Phe29, which are critical for the Pex3p binding and peroxisome biogenesis.
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==Disease==
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Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p.,Sato Y, Shibata H, Nakatsu T, Nakano H, Kashiwayama Y, Imanaka T, Kato H EMBO J. 2010 Dec 15;29(24):4083-93. Epub 2010 Nov 19. PMID:21102411<ref>PMID:21102411</ref>
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[[http://www.uniprot.org/uniprot/Q6FGP5_HUMAN Q6FGP5_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.
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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/Q6FGP5_HUMAN Q6FGP5_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>
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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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[[3ajb]] is a 2 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=3AJB OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:021102411</ref><references group="xtra"/><references/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Kato, H.]]
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[[Category: Kato, H]]
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[[Category: Nakatsu, T.]]
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[[Category: Nakatsu, T]]
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[[Category: Sato, Y.]]
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[[Category: Sato, Y]]
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[[Category: Shibata, H.]]
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[[Category: Shibata, H]]
[[Category: All alpha]]
[[Category: All alpha]]
[[Category: Protein transport]]
[[Category: Protein transport]]
[[Category: Protein-protein complex]]
[[Category: Protein-protein complex]]

Revision as of 14:19, 18 December 2014

Crystal Structure of human Pex3p in complex with N-terminal Pex19p peptide

3ajb, resolution 2.50Å

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