8af0

From Proteopedia

(Difference between revisions)

Revision as of 06:58, 14 September 2022

Crystal structure of human angiogenin and RNA duplex

Structural highlights

8af0 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ANGI_HUMAN] Defects in ANG are the cause of susceptibility to amyotrophic lateral sclerosis type 9 (ALS9) [MIM: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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Function

[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.^[7] ^[8]

Publication Abstract from PubMed

Angiogenin is an unusual member of the RNase A family and is of great interest in multiple pathological contexts. Although it has been assigned various regulatory roles, its core catalytic function is that of an RNA endonuclease. However, its catalytic efficiency is comparatively low and this has been linked to a unique C-terminal helix which partially blocks its RNA-binding site. Assuming that binding to its RNA substrate could trigger a conformational rearrangement, much speculation has arisen on the topic of the interaction of angiogenin with RNA. To date, no structural data on angiogenin-RNA interactions have been available. Here, the structure of angiogenin bound to a double-stranded RNA duplex is reported. The RNA does not reach the active site of angiogenin and no structural arrangement of the C-terminal domain is observed. However, angiogenin forms a previously unobserved crystallographic dimer that makes several backbone interactions with the major and minor grooves of the RNA double helix.

Structure of angiogenin dimer bound to double-stranded RNA.,Sievers K, Ficner R Acta Crystallogr F Struct Biol Commun. 2022 Sep 1;78(Pt 9):330-337. doi:, 10.1107/S2053230X22008317. Epub 2022 Aug 30. PMID:36048083^[9]

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

References

↑ Wu D, Yu W, Kishikawa H, Folkerth RD, Iafrate AJ, Shen Y, Xin W, Sims K, Hu GF. Angiogenin loss-of-function mutations in amyotrophic lateral sclerosis. Ann Neurol. 2007 Dec;62(6):609-17. PMID:17886298 doi:10.1002/ana.21221
↑ Greenway MJ, Alexander MD, Ennis S, Traynor BJ, Corr B, Frost E, Green A, Hardiman O. A novel candidate region for ALS on chromosome 14q11.2. Neurology. 2004 Nov 23;63(10):1936-8. PMID:15557516
↑ Greenway MJ, Andersen PM, Russ C, Ennis S, Cashman S, Donaghy C, Patterson V, Swingler R, Kieran D, Prehn J, Morrison KE, Green A, Acharya KR, Brown RH Jr, Hardiman O. ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. Nat Genet. 2006 Apr;38(4):411-3. Epub 2006 Feb 26. PMID:16501576 doi:10.1038/ng1742
↑ Crabtree B, Thiyagarajan N, Prior SH, Wilson P, Iyer S, Ferns T, Shapiro R, Brew K, Subramanian V, Acharya KR. Characterization of human angiogenin variants implicated in amyotrophic lateral sclerosis. Biochemistry. 2007 Oct 23;46(42):11810-8. Epub 2007 Sep 27. PMID:17900154 doi:10.1021/bi701333h
↑ Gellera C, Colombrita C, Ticozzi N, Castellotti B, Bragato C, Ratti A, Taroni F, Silani V. Identification of new ANG gene mutations in a large cohort of Italian patients with amyotrophic lateral sclerosis. Neurogenetics. 2008 Feb;9(1):33-40. Epub 2007 Dec 18. PMID:18087731 doi:10.1007/s10048-007-0111-3
↑ Conforti FL, Sprovieri T, Mazzei R, Ungaro C, La Bella V, Tessitore A, Patitucci A, Magariello A, Gabriele AL, Tedeschi G, Simone IL, Majorana G, Valentino P, Condino F, Bono F, Monsurro MR, Muglia M, Quattrone A. A novel Angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy. Neuromuscul Disord. 2008 Jan;18(1):68-70. Epub 2007 Aug 20. PMID:17703939 doi:S0960-8966(07)00676-1
↑ Saxena SK, Rybak SM, Davey RT Jr, Youle RJ, Ackerman EJ. Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily. J Biol Chem. 1992 Oct 25;267(30):21982-6. PMID:1400510
↑ Dickson KA, Kang DK, Kwon YS, Kim JC, Leland PA, Kim BM, Chang SI, Raines RT. Ribonuclease inhibitor regulates neovascularization by human angiogenin. Biochemistry. 2009 May 12;48(18):3804-6. doi: 10.1021/bi9005094. PMID:19354288 doi:10.1021/bi9005094
↑ Sievers K, Ficner R. Structure of angiogenin dimer bound to double-stranded RNA. Acta Crystallogr F Struct Biol Commun. 2022 Sep 1;78(Pt 9):330-337. doi:, 10.1107/S2053230X22008317. Epub 2022 Aug 30. PMID:36048083 doi:http://dx.doi.org/10.1107/S2053230X22008317

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/8af0"

Categories: Homo sapiens | Large Structures | Ficner R | Sievers K

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8af0 is ON HOLD
+==Crystal structure of human angiogenin and RNA duplex==
+<StructureSection load='8af0' size='340' side='right'caption='[[8af0]], [[Resolution|resolution]] 2.43&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8af0]] 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=8AF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AF0 FirstGlance]. <br>
+</td></tr><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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8af0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8af0 OCA], [https://pdbe.org/8af0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8af0 RCSB], [https://www.ebi.ac.uk/pdbsum/8af0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8af0 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 ==
+Angiogenin is an unusual member of the RNase A family and is of great interest in multiple pathological contexts. Although it has been assigned various regulatory roles, its core catalytic function is that of an RNA endonuclease. However, its catalytic efficiency is comparatively low and this has been linked to a unique C-terminal helix which partially blocks its RNA-binding site. Assuming that binding to its RNA substrate could trigger a conformational rearrangement, much speculation has arisen on the topic of the interaction of angiogenin with RNA. To date, no structural data on angiogenin-RNA interactions have been available. Here, the structure of angiogenin bound to a double-stranded RNA duplex is reported. The RNA does not reach the active site of angiogenin and no structural arrangement of the C-terminal domain is observed. However, angiogenin forms a previously unobserved crystallographic dimer that makes several backbone interactions with the major and minor grooves of the RNA double helix.
-Authors:
+Structure of angiogenin dimer bound to double-stranded RNA.,Sievers K, Ficner R Acta Crystallogr F Struct Biol Commun. 2022 Sep 1;78(Pt 9):330-337. doi:, 10.1107/S2053230X22008317. Epub 2022 Aug 30. PMID:36048083<ref>PMID:36048083</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8af0" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Ficner R]]
+[[Category: Sievers K]]

8af0

From Proteopedia

Revision as of 06:58, 14 September 2022

Crystal structure of human angiogenin and RNA duplex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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