2r0o

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[[Image:2r0o.jpg|left|200px]]
 
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{{Structure
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==Crystal structure of the actin-binding domain of human alpha-actinin-4 mutant(K255E)==
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|PDB= 2r0o |SIZE=350|CAPTION= <scene name='initialview01'>2r0o</scene>, resolution 2.20&Aring;
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<StructureSection load='2r0o' size='340' side='right'caption='[[2r0o]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:Gol+Binding+Site+For+Residue+A+1'>AC1</scene>, <scene name='pdbsite=AC2:Gol+Binding+Site+For+Residue+B+2'>AC2</scene> and <scene name='pdbsite=AC3:Gol+Binding+Site+For+Residue+B+3'>AC3</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
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<table><tr><td colspan='2'>[[2r0o]] is a 2 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=2R0O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R0O FirstGlance]. <br>
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|ACTIVITY=
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</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>
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|GENE= ACTN4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2r0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r0o OCA], [https://pdbe.org/2r0o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r0o RCSB], [https://www.ebi.ac.uk/pdbsum/2r0o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r0o ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r0o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r0o OCA], [http://www.ebi.ac.uk/pdbsum/2r0o PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2r0o RCSB]</span>
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== Disease ==
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}}
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[https://www.uniprot.org/uniprot/ACTN4_HUMAN ACTN4_HUMAN] Defects in ACTN4 are the cause of focal segmental glomerulosclerosis type 1 (FSGS1) [MIM:[https://omim.org/entry/603278 603278]. A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and edema. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.<ref>PMID:10700177</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/ACTN4_HUMAN ACTN4_HUMAN] F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r0/2r0o_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2r0o ConSurf].
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<div style="clear:both"></div>
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'''Crystal structure of the actin-binding domain of human alpha-actinin-4 mutant(K255E)'''
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==See Also==
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*[[Actinin 3D structures|Actinin 3D structures]]
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== References ==
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==Overview==
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<references/>
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Mutations in alpha-actinin-4 have been linked to familial focal segmental glomerulosclerosis (FSGS), a common renal disorder in humans, and produce an apparent increase in the actin-binding affinity of alpha-actinin-4 in vitro. One of the mutations, in particular, Lys255Glu, falls in the middle of the actin-binding interface of the actin-binding domain (ABD). The ABD consists of tandem calponin homology (CH) domains (CH1 and CH2). The crystal structures of most ABDs display a compact conformation, characterized by extensive inter-CH interactions. However, the conformation of F-actin-bound ABDs is unsettled. Some electron microscopy studies find that the compact conformation is preserved upon binding to F-actin, whereas other studies suggest that the CHs separate and the ABD becomes extended. The Lys255Glu mutation in CH2 is significant in this regard since it removes a crucial inter-CH interaction with Trp147 of CH1, thought to stabilize the compact conformation. Together, the increased actin-binding affinity and the removal of this important inter-CH contact suggested that the Lys255Glu mutation might facilitate the transition toward the open ABD conformation proposed by some of the electron microscopy studies. However, the crystal structure of the ABD of alpha-actinin-4 Lys255Glu mutant described here displays the canonical compact conformation. Furthermore, the sedimentation coefficients by analytical ultracentrifugation of wild-type and FSGS mutant ABDs (Lys255Glu, Ser262Pro, and Thr259Ile) are nearly identical (2.50+/-0.03 S) and are in good agreement with the theoretical value calculated from the crystal structure (2.382 S), implying that the compact conformation is retained in solution. The absence of a structural change suggests that the compact ABD conformation observed in the majority of the structures is highly stable and is preserved in solution, even in FSGS mutant ABDs.
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: Glomerulosclerosis, focal segmental, 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604638 604638]]
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==About this Structure==
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2R0O is a [[Single protein]] structure of 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=2R0O OCA].
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==Reference==
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Crystal structure of the actin-binding domain of alpha-actinin-4 Lys255Glu mutant implicated in focal segmental glomerulosclerosis., Lee SH, Weins A, Hayes DB, Pollak MR, Dominguez R, J Mol Biol. 2008 Feb 15;376(2):317-24. Epub 2007 Dec 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18164029 18164029]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Dominguez, R.]]
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[[Category: Dominguez R]]
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[[Category: Lee, S H.]]
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[[Category: Lee SH]]
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[[Category: actin-binding protein]]
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[[Category: actin-crosslinking]]
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[[Category: calcium]]
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[[Category: calponin homology domain]]
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[[Category: ch domain]]
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[[Category: cytoplasm]]
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[[Category: disease mutation]]
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[[Category: glomeruloscleros spectrin family]]
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[[Category: nucleus]]
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[[Category: phosphorylation]]
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[[Category: structural protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:55:19 2008''
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Current revision

Crystal structure of the actin-binding domain of human alpha-actinin-4 mutant(K255E)

PDB ID 2r0o

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