1fch: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1fch.gif|left|200px]]<br />
-<applet load="1fch" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1fch, resolution 2.20&Aring;" />
-'''CRYSTAL STRUCTURE OF THE PTS1 COMPLEXED TO THE TPR REGION OF HUMAN PEX5'''<br />
-==Overview==
+==CRYSTAL STRUCTURE OF THE PTS1 COMPLEXED TO THE TPR REGION OF HUMAN PEX5==
-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.
+<StructureSection load='1fch' size='340' side='right'caption='[[1fch]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
-==Disease==
+<table><tr><td colspan='2'>[[1fch]] 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=1FCH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FCH FirstGlance]. <br>
-Known diseases associated with this structure: Adrenoleukodystrophy, neonatal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600414 600414]], Zellweger syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600414 600414]]
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</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>
-==About this Structure==
+</table>
-FCH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FCH OCA].
+== 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.
-==Reference==
+== Function ==
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11101887 11101887]
+[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].
+<div style="clear:both"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Berg, J.M.]]
+[[Category: Berg JM]]
-[[Category: Geisbrecht, B.V.]]
+[[Category: Gatto Jr GJ]]
-[[Category: Gould, S.J.]]
+[[Category: Geisbrecht BV]]
-[[Category: Jr., G.J.Gatto.]]
+[[Category: Gould SJ]]
-[[Category: helical repeat]]
-[[Category: protein-peptide complex]]
-[[Category: tetratricopeptide repeat]]
-[[Category: tpr]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:51:30 2007''