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==R121H - Angiogenin mutants and amyotrophic lateral sclerosis - a biochemical and biological analysis== | |||
<StructureSection load='4ahn' size='340' side='right'caption='[[4ahn]], [[Resolution|resolution]] 2.98Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ahn]] 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=4AHN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AHN 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]] 2.977Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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=4ahn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ahn OCA], [https://pdbe.org/4ahn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ahn RCSB], [https://www.ebi.ac.uk/pdbsum/4ahn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ahn ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/ANGI_HUMAN ANGI_HUMAN] Defects in ANG are the cause of susceptibility to amyotrophic lateral sclerosis type 9 (ALS9) [MIM:[https://omim.org/entry/611895 611895]. ALS is a degenerative disorder of motor neurons in the cortex, brain stem and spinal cord. ALS is characterized by muscular weakness and atrophy.<ref>PMID:17886298</ref> <ref>PMID:15557516</ref> <ref>PMID:16501576</ref> <ref>PMID:17900154</ref> <ref>PMID:18087731</ref> <ref>PMID:17703939</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ANGI_HUMAN ANGI_HUMAN] May function as a tRNA-specific ribonuclease that abolishes protein synthesis by specifically hydrolyzing cellular tRNAs. Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo.<ref>PMID:1400510</ref> <ref>PMID:19354288</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mutations in angiogenin (ANG), a member of the ribonuclease A superfamily, are associated with amyotrophic lateral sclerosis (ALS; sporadic and familial) and Parkinson's disease. We have previously shown that ANG is expressed in neurons during neuro-ectodermal differentiation, and that it has both neurotrophic and neuroprotective functions. Here we report the atomic resolution structure of native ANG and 11 ANG-ALS variants. We correlate the structural changes to the effects on neuronal survival and the ability to induce stress granules in neuronal cell lines. ANG-ALS variants that affect the structure of the catalytic site and either decrease or increase the RNase activity affect neuronal survival. Neuronal cell lines expressing the ANG-ALS variants also lack the ability to form stress granules. Our structure-function studies on these ANG-ALS variants are the first to provide insights into the cellular and molecular mechanisms underlying their role in ALS. | |||
Structural and molecular insights into the mechanism of action of human angiogenin-ALS variants in neurons.,Thiyagarajan N, Ferguson R, Subramanian V, Acharya KR Nat Commun. 2012 Oct 9;3:1121. doi: 10.1038/ncomms2126. PMID:23047679<ref>PMID:23047679</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4ahn" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
[[ | *[[Ribonuclease 3D structures|Ribonuclease 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Acharya | [[Category: Large Structures]] | ||
[[Category: Ferguson | [[Category: Acharya KR]] | ||
[[Category: Pham | [[Category: Ferguson R]] | ||
[[Category: Saha | [[Category: Pham T]] | ||
[[Category: Subramanian | [[Category: Saha S]] | ||
[[Category: Thiyagarajan | [[Category: Subramanian V]] | ||
[[Category: Thiyagarajan N]] | |||