3p56

From Proteopedia

(Difference between revisions)

Current revision

The structure of the human RNase H2 complex defines key interaction interfaces relevant to enzyme function and human disease

Structural highlights

3p56 is a 6 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 4.06Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

RNH2A_HUMAN Aicardi-Goutieres syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

RNH2A_HUMAN Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.^[1] ^[2]

Publication Abstract from PubMed

Ribonuclease H2 (RNase H2) is the major nuclear enzyme involved in the degradation of RNA/DNA hybrids and removal of ribonucleotides misincorporated in genomic DNA. Mutations in each of the three RNase H2 subunits have been implicated in a human auto-inflammatory disorder, Aicardi-Goutieres Syndrome (AGS). To understand how mutations impact on RNase H2 function we determined the crystal structure of the human heterotrimer. In doing so, we correct several key regions of the previously reported murine RNase H2 atomic model and provide biochemical validation for our structural model. Our results provide new insights into how the subunits are arranged to form an enzymatically active complex. In particular, we establish that the RNASEH2A C terminus is a eukaryotic adaptation for binding the two accessory subunits, with residues within it required for enzymatic activity. This C-terminal extension interacts with the RNASEH2C C terminus and both are necessary to form a stable, enzymatically active heterotrimer. Disease mutations cluster at this interface between all three subunits, destabilizing the complex and/or impairing enzyme activity. Altogether, we locate 25 out of 29 residues mutated in AGS patients, establishing a firm basis for future investigations into disease pathogenesis and function of the RNase H2 enzyme.

The Structure of the Human RNase H2 Complex Defines Key Interaction Interfaces Relevant to Enzyme Function and Human Disease.,Reijns MA, Bubeck D, Gibson LC, Graham SC, Baillie GS, Jones EY, Jackson AP J Biol Chem. 2011 Mar 25;286(12):10530-9. Epub 2010 Dec 22. PMID:21177854^[3]

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

References

↑ Crow YJ, Leitch A, Hayward BE, Garner A, Parmar R, Griffith E, Ali M, Semple C, Aicardi J, Babul-Hirji R, Baumann C, Baxter P, Bertini E, Chandler KE, Chitayat D, Cau D, Dery C, Fazzi E, Goizet C, King MD, Klepper J, Lacombe D, Lanzi G, Lyall H, Martinez-Frias ML, Mathieu M, McKeown C, Monier A, Oade Y, Quarrell OW, Rittey CD, Rogers RC, Sanchis A, Stephenson JB, Tacke U, Till M, Tolmie JL, Tomlin P, Voit T, Weschke B, Woods CG, Lebon P, Bonthron DT, Ponting CP, Jackson AP. Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection. Nat Genet. 2006 Aug;38(8):910-6. Epub 2006 Jul 16. PMID:16845400 doi:http://dx.doi.org/10.1038/ng1842
↑ Figiel M, Chon H, Cerritelli SM, Cybulska M, Crouch RJ, Nowotny M. The structural and biochemical characterization of human RNase H2 complex reveals the molecular basis for substrate recognition and Aicardi-Goutieres syndrome defects. J Biol Chem. 2011 Mar 25;286(12):10540-50. Epub 2010 Dec 22. PMID:21177858 doi:10.1074/jbc.M110.181974
↑ Reijns MA, Bubeck D, Gibson LC, Graham SC, Baillie GS, Jones EY, Jackson AP. The Structure of the Human RNase H2 Complex Defines Key Interaction Interfaces Relevant to Enzyme Function and Human Disease. J Biol Chem. 2011 Mar 25;286(12):10530-9. Epub 2010 Dec 22. PMID:21177854 doi:10.1074/jbc.M110.177394

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3p56"

Categories: Homo sapiens | Large Structures | Bubeck D | Graham SC | Jones EY

@@ Line 3: / Line 3: @@
 <StructureSection load='3p56' size='340' side='right'caption='[[3p56]], [[Resolution|resolution]] 4.06&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3p56]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P56 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3p56]] is a 6 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=3P56 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P56 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3p5j|3p5j]], [[3kio|3kio]]</div></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]] 4.06&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNASEH2A, RNASEHI, RNHIA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DLEU8, RNASEH2B ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), AYP1, RNASEH2C ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ribonuclease_H Ribonuclease H], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.26.4 3.1.26.4] </span></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=3p56 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p56 OCA], [https://pdbe.org/3p56 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p56 RCSB], [https://www.ebi.ac.uk/pdbsum/3p56 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p56 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/RNH2A_HUMAN RNH2A_HUMAN]] Aicardi-Goutieres syndrome. The disease is caused by mutations affecting the gene represented in this entry. [[https://www.uniprot.org/uniprot/RNH2C_HUMAN RNH2C_HUMAN]] Aicardi-Goutieres syndrome. The disease is caused by mutations affecting the gene represented in this entry. [[https://www.uniprot.org/uniprot/RNH2B_HUMAN RNH2B_HUMAN]] Aicardi-Goutieres syndrome. The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/RNH2A_HUMAN RNH2A_HUMAN] Aicardi-Goutieres syndrome. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[https://www.uniprot.org/uniprot/RNH2A_HUMAN RNH2A_HUMAN]] Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.<ref>PMID:16845400</ref> <ref>PMID:21177858</ref>  [[https://www.uniprot.org/uniprot/RNH2C_HUMAN RNH2C_HUMAN]] Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.<ref>PMID:16845400</ref> <ref>PMID:21177858</ref>  [[https://www.uniprot.org/uniprot/RNH2B_HUMAN RNH2B_HUMAN]] Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.<ref>PMID:21177858</ref> <ref>PMID:16845400</ref>
+[https://www.uniprot.org/uniprot/RNH2A_HUMAN RNH2A_HUMAN] Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.<ref>PMID:16845400</ref> <ref>PMID:21177858</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 29: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ribonuclease H]]
+[[Category: Bubeck D]]
-[[Category: Bubeck, D]]
+[[Category: Graham SC]]
-[[Category: Graham, S C]]
+[[Category: Jones EY]]
-[[Category: Jones, E Y]]
-[[Category: Hydrolase-replication complex]]
-[[Category: Nuclease that cleaves rna/dna hybrid]]
-[[Category: Nucleus]]
-[[Category: Rnase h fold]]
-[[Category: Triple beta-barrel]]

3p56

From Proteopedia

Current revision

The structure of the human RNase H2 complex defines key interaction interfaces relevant to enzyme function and human disease

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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