View source for 1fch


==CRYSTAL STRUCTURE OF THE PTS1 COMPLEXED TO THE TPR REGION OF HUMAN PEX5==
<StructureSection load='1fch' size='340' side='right'caption='[[1fch]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1fch]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FCH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FCH FirstGlance]. <br>
</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=1fch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fch OCA], [https://pdbe.org/1fch PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fch RCSB], [https://www.ebi.ac.uk/pdbsum/1fch PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fch 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/fc/1fch_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=1fch ConSurf].
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== Publication Abstract from PubMed ==
Many proteins contain targeting signals within their sequences that specify their delivery to particular organelles. The peroxisomal targeting signal-1 (PTS1) is a C-terminal tripeptide that is sufficient to direct proteins into peroxisomes. The PTS1 sequence closely approximates Ser-Lys-Leu-COO-. PEX5, the receptor for PTS1, interacts with the signal via a series of tetratricopeptide repeats (TPRs) within its C-terminal half. Here we report the crystal structure of a fragment of human PEX5 that includes all seven predicted TPR motifs in complex with a pentapeptide containing a PTS1 sequence. Two clusters of three TPRs almost completely surround the peptide, while a hinge region, previously identified as TPR4, forms a distinct structure that enables the two sets of TPRs to form a single binding site. This structure reveals the molecular basis for PTS1 recognition and demonstrates a novel mode of TPR-peptide interaction.

Peroxisomal targeting signal-1 recognition by the TPR domains of human PEX5.,Gatto GJ Jr, Geisbrecht BV, Gould SJ, Berg JM Nat Struct Biol. 2000 Dec;7(12):1091-5. PMID:11101887<ref>PMID:11101887</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1fch" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Berg, J M]]
[[Category: Gatto, G J]]
[[Category: Geisbrecht, B V]]
[[Category: Gould, S J]]
[[Category: Helical repeat]]
[[Category: Protein-peptide complex]]
[[Category: Signaling protein]]
[[Category: Tetratricopeptide repeat]]
[[Category: Tpr]]