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| - | {{STRUCTURE_2c0m| PDB=2c0m | SCENE= }} | |
| - | ===APO FORM OF THE TPR DOMAIN OF THE PEX5P RECEPTOR=== | |
| - | {{ABSTRACT_PUBMED_17157249}} | |
| | | | |
| - | ==Disease== | + | ==apo form of the TPR domain of the pex5p receptor== |
| - | [[http://www.uniprot.org/uniprot/PEX5_HUMAN PEX5_HUMAN]] Defects in PEX5 are the cause of peroxisome biogenesis disorder 2A (PBD2A) [MIM:[http://omim.org/entry/214110 214110]]. A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and characterized clinically 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.<ref>PMID:7719337</ref> Defects in PEX5 are the cause of peroxisome biogenesis disorder 2B (PBD2B) [MIM:[http://omim.org/entry/202370 202370]]. A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid. | + | <StructureSection load='2c0m' size='340' side='right'caption='[[2c0m]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[2c0m]] is a 4 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=2C0M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C0M FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</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=2c0m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c0m OCA], [https://pdbe.org/2c0m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c0m RCSB], [https://www.ebi.ac.uk/pdbsum/2c0m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c0m ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/PEX5_HUMAN PEX5_HUMAN] Defects in PEX5 are the cause of peroxisome biogenesis disorder 2A (PBD2A) [MIM:[https://omim.org/entry/214110 214110]. A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and characterized clinically 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.<ref>PMID:7719337</ref> Defects in PEX5 are the cause of peroxisome biogenesis disorder 2B (PBD2B) [MIM:[https://omim.org/entry/202370 202370]. A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PEX5_HUMAN PEX5_HUMAN] Binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import.<ref>PMID:7719337</ref> <ref>PMID:7790377</ref> <ref>PMID:7706321</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c0/2c0m_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </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=2c0m ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Peroxisomes require the translocation of folded and functional target proteins of various sizes across the peroxisomal membrane. We have investigated the structure and function of the principal import receptor Pex5p, which recognizes targets bearing a C-terminal peroxisomal targeting signal type 1. Crystal structures of the receptor in the presence and absence of a peroxisomal target, sterol carrier protein 2, reveal major structural changes from an open, snail-like conformation into a closed, circular conformation. These changes are caused by a long loop C terminal to the 7-fold tetratricopeptide repeat segments. Mutations in residues of this loop lead to defects in peroxisomal import in human fibroblasts. The structure of the receptor/cargo complex demonstrates that the primary receptor-binding site of the cargo is structurally and topologically autonomous, enabling the cargo to retain its native structure and function. |
| | | | |
| - | ==Function==
| + | Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p.,Stanley WA, Filipp FV, Kursula P, Schuller N, Erdmann R, Schliebs W, Sattler M, Wilmanns M Mol Cell. 2006 Dec 8;24(5):653-63. PMID:17157249<ref>PMID:17157249</ref> |
| - | [[http://www.uniprot.org/uniprot/PEX5_HUMAN PEX5_HUMAN]] Binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import.<ref>PMID:7719337</ref><ref>PMID:7790377</ref><ref>PMID:7706321</ref>
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[2c0m]] is a 4 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=2C0M OCA].
| + | </div> |
| - | | + | <div class="pdbe-citations 2c0m" style="background-color:#fffaf0;"></div> |
| - | ==Reference==
| + | == References == |
| - | <ref group="xtra">PMID:017157249</ref><references group="xtra"/><references/> | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Kursula, P.]] | + | [[Category: Large Structures]] |
| - | [[Category: Stanley, W A.]] | + | [[Category: Kursula P]] |
| - | [[Category: Wilmanns, M.]] | + | [[Category: Stanley WA]] |
| - | [[Category: Disease mutation]] | + | [[Category: Wilmanns M]] |
| - | [[Category: Import receptor complex]]
| + | |
| - | [[Category: Peroxisome]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| - | [[Category: Tpr repeat]]
| + | |
| - | [[Category: Transport]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| - | [[Category: Zellweger syndrome]]
| + | |
| Structural highlights
Disease
PEX5_HUMAN Defects in PEX5 are the cause of peroxisome biogenesis disorder 2A (PBD2A) [MIM:214110. A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and characterized clinically 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.[1] Defects in PEX5 are the cause of peroxisome biogenesis disorder 2B (PBD2B) [MIM:202370. A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid.
Function
PEX5_HUMAN Binds to the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) and plays an essential role in peroxisomal protein import.[2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Peroxisomes require the translocation of folded and functional target proteins of various sizes across the peroxisomal membrane. We have investigated the structure and function of the principal import receptor Pex5p, which recognizes targets bearing a C-terminal peroxisomal targeting signal type 1. Crystal structures of the receptor in the presence and absence of a peroxisomal target, sterol carrier protein 2, reveal major structural changes from an open, snail-like conformation into a closed, circular conformation. These changes are caused by a long loop C terminal to the 7-fold tetratricopeptide repeat segments. Mutations in residues of this loop lead to defects in peroxisomal import in human fibroblasts. The structure of the receptor/cargo complex demonstrates that the primary receptor-binding site of the cargo is structurally and topologically autonomous, enabling the cargo to retain its native structure and function.
Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p.,Stanley WA, Filipp FV, Kursula P, Schuller N, Erdmann R, Schliebs W, Sattler M, Wilmanns M Mol Cell. 2006 Dec 8;24(5):653-63. PMID:17157249[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dodt G, Braverman N, Wong C, Moser A, Moser HW, Watkins P, Valle D, Gould SJ. Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders. Nat Genet. 1995 Feb;9(2):115-25. PMID:7719337 doi:http://dx.doi.org/10.1038/ng0295-115
- ↑ Dodt G, Braverman N, Wong C, Moser A, Moser HW, Watkins P, Valle D, Gould SJ. Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders. Nat Genet. 1995 Feb;9(2):115-25. PMID:7719337 doi:http://dx.doi.org/10.1038/ng0295-115
- ↑ Wiemer EA, Nuttley WM, Bertolaet BL, Li X, Francke U, Wheelock MJ, Anne UK, Johnson KR, Subramani S. Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders. J Cell Biol. 1995 Jul;130(1):51-65. PMID:7790377
- ↑ Fransen M, Brees C, Baumgart E, Vanhooren JC, Baes M, Mannaerts GP, Van Veldhoven PP. Identification and characterization of the putative human peroxisomal C-terminal targeting signal import receptor. J Biol Chem. 1995 Mar 31;270(13):7731-6. PMID:7706321
- ↑ Stanley WA, Filipp FV, Kursula P, Schuller N, Erdmann R, Schliebs W, Sattler M, Wilmanns M. Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p. Mol Cell. 2006 Dec 8;24(5):653-63. PMID:17157249 doi:10.1016/j.molcel.2006.10.024
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