3o55

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human FAD-linked augmenter of liver regeneration (ALR)

Structural highlights

3o55 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ALR_HUMAN Congenital cataract - progressive muscular hypotonia - hearing loss - developmental delay. The disease is caused by mutations affecting the gene represented in this entry.

Function

ALR_HUMAN Isoform 1: FAD-dependent sulfhydryl oxidase that regenerates the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen.^[1] ^[2] ^[3] ^[4] ^[5] Isoform 2: May act as an autocrine hepatotrophic growth factor promoting liver regeneration.^[6] ^[7] ^[8] ^[9] ^[10]

Publication Abstract from PubMed

Oxidative protein folding in the mitochondrial intermembrane space requires the transfer of a disulfide bond from MIA40 to the substrate. During this process MIA40 is reduced and regenerated to a functional state through the interaction with the flavin-dependent sulfhydryl oxidase ALR. Here we present the mechanistic basis of ALR-MIA40 interaction at atomic resolution by biochemical and structural analyses of the mitochondrial ALR isoform and its covalent mixed disulfide intermediate with MIA40. This ALR isoform contains a folded FAD-binding domain at the C-terminus and an unstructured, flexible N-terminal domain, weakly and transiently interacting one with the other. A specific region of the N-terminal domain guides the interaction with the MIA40 substrate binding cleft (mimicking the interaction of the substrate itself), without being involved in the import of ALR. The hydrophobicity-driven binding of this region ensures precise protein-protein recognition needed for an efficient electron transfer process.

Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR.,Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Kallergi E, Lionaki E, Pozidis C, Tokatlidis K Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4811-6. Epub 2011 Mar 7. PMID:21383138^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Daithankar VN, Farrell SR, Thorpe C. Augmenter of liver regeneration: substrate specificity of a flavin-dependent oxidoreductase from the mitochondrial intermembrane space. Biochemistry. 2009 Jun 9;48(22):4828-37. doi: 10.1021/bi900347v. PMID:19397338 doi:http://dx.doi.org/10.1021/bi900347v
↑ Sztolsztener ME, Brewinska A, Guiard B, Chacinska A. Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40. Traffic. 2013 Mar;14(3):309-20. doi: 10.1111/tra.12030. Epub 2012 Dec 16. PMID:23186364 doi:http://dx.doi.org/10.1111/tra.12030
↑ Daithankar VN, Schaefer SA, Dong M, Bahnson BJ, Thorpe C. Structure of the human sulfhydryl oxidase augmenter of liver regeneration and characterization of a human mutation causing an autosomal recessive myopathy. Biochemistry. 2010 Jul 1. PMID:20593814 doi:10.1021/bi100912m
↑ Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Kallergi E, Lionaki E, Pozidis C, Tokatlidis K. Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4811-6. Epub 2011 Mar 7. PMID:21383138 doi:10.1073/pnas.1014542108
↑ Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Tokatlidis K. An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR. J Am Chem Soc. 2012 Jan 25;134(3):1442-5. Epub 2012 Jan 6. PMID:22224850 doi:10.1021/ja209881f
↑ Daithankar VN, Farrell SR, Thorpe C. Augmenter of liver regeneration: substrate specificity of a flavin-dependent oxidoreductase from the mitochondrial intermembrane space. Biochemistry. 2009 Jun 9;48(22):4828-37. doi: 10.1021/bi900347v. PMID:19397338 doi:http://dx.doi.org/10.1021/bi900347v
↑ Sztolsztener ME, Brewinska A, Guiard B, Chacinska A. Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40. Traffic. 2013 Mar;14(3):309-20. doi: 10.1111/tra.12030. Epub 2012 Dec 16. PMID:23186364 doi:http://dx.doi.org/10.1111/tra.12030
↑ Daithankar VN, Schaefer SA, Dong M, Bahnson BJ, Thorpe C. Structure of the human sulfhydryl oxidase augmenter of liver regeneration and characterization of a human mutation causing an autosomal recessive myopathy. Biochemistry. 2010 Jul 1. PMID:20593814 doi:10.1021/bi100912m
↑ Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Kallergi E, Lionaki E, Pozidis C, Tokatlidis K. Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4811-6. Epub 2011 Mar 7. PMID:21383138 doi:10.1073/pnas.1014542108
↑ Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Tokatlidis K. An electron-transfer path through an extended disulfide relay system: the case of the redox protein ALR. J Am Chem Soc. 2012 Jan 25;134(3):1442-5. Epub 2012 Jan 6. PMID:22224850 doi:10.1021/ja209881f
↑ Banci L, Bertini I, Calderone V, Cefaro C, Ciofi-Baffoni S, Gallo A, Kallergi E, Lionaki E, Pozidis C, Tokatlidis K. Molecular recognition and substrate mimicry drive the electron-transfer process between MIA40 and ALR. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4811-6. Epub 2011 Mar 7. PMID:21383138 doi:10.1073/pnas.1014542108

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3o55"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human FAD-linked augmenter of liver regeneration (ALR)==
-<StructureSection load='3o55' size='340' side='right' caption='[[3o55]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='3o55' size='340' side='right'caption='[[3o55]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3o55]] is a 1 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=3O55 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O55 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3o55]] is a 1 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=3O55 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O55 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></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]] 1.9&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mbg|3mbg]], [[2hj3|2hj3]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3o55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o55 OCA], [https://pdbe.org/3o55 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o55 RCSB], [https://www.ebi.ac.uk/pdbsum/3o55 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o55 ProSAT]</span></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=3o55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o55 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o55 RCSB], [http://www.ebi.ac.uk/pdbsum/3o55 PDBsum]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ALR_HUMAN ALR_HUMAN] Congenital cataract - progressive muscular hypotonia - hearing loss - developmental delay. The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/ALR_HUMAN ALR_HUMAN] Isoform 1: FAD-dependent sulfhydryl oxidase that regenerates the redox-active disulfide bonds in CHCHD4/MIA40, a chaperone essential for disulfide bond formation and protein folding in the mitochondrial intermembrane space. The reduced form of CHCHD4/MIA40 forms a transient intermolecular disulfide bridge with GFER/ERV1, resulting in regeneration of the essential disulfide bonds in CHCHD4/MIA40, while GFER/ERV1 becomes re-oxidized by donating electrons to cytochrome c or molecular oxygen.<ref>PMID:19397338</ref> <ref>PMID:23186364</ref> <ref>PMID:20593814</ref> <ref>PMID:21383138</ref> <ref>PMID:22224850</ref>   Isoform 2: May act as an autocrine hepatotrophic growth factor promoting liver regeneration.<ref>PMID:19397338</ref> <ref>PMID:23186364</ref> <ref>PMID:20593814</ref> <ref>PMID:21383138</ref> <ref>PMID:22224850</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3o55" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 21: / Line 26: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Banci, L]]
+[[Category: Large Structures]]
-[[Category: Bertini, I]]
+[[Category: Banci L]]
-[[Category: Calderone, V]]
+[[Category: Bertini I]]
-[[Category: Cefaro, C]]
+[[Category: Calderone V]]
-[[Category: Ciofi-Baffoni, S]]
+[[Category: Cefaro C]]
-[[Category: Gallo, A]]
+[[Category: Ciofi-Baffoni S]]
-[[Category: Kallergi, E]]
+[[Category: Gallo A]]
-[[Category: Lionaki, E]]
+[[Category: Kallergi E]]
-[[Category: Pozidis, C]]
+[[Category: Lionaki E]]
-[[Category: Tokatlidis, K]]
+[[Category: Pozidis C]]
-[[Category: Alr]]
+[[Category: Tokatlidis K]]
-[[Category: Fad]]
-[[Category: Flavin]]
-[[Category: Flavoprotein]]
-[[Category: Gfer]]
-[[Category: Sulfhydryl oxidase]]

3o55

From Proteopedia

Current revision

Crystal structure of human FAD-linked augmenter of liver regeneration (ALR)

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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