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| | <StructureSection load='3p5j' size='340' side='right'caption='[[3p5j]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='3p5j' size='340' side='right'caption='[[3p5j]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3p5j]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P5J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P5J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3p5j]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P5J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P5J 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;'>[[3p56|3p56]], [[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]] 2.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rnaseh2a, Rnasehi ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Rnaseh2b, Dleu8 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Rnaseh2c, Ayp1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
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| - | <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>
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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=3p5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p5j OCA], [https://pdbe.org/3p5j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p5j RCSB], [https://www.ebi.ac.uk/pdbsum/3p5j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p5j ProSAT]</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=3p5j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p5j OCA], [https://pdbe.org/3p5j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p5j RCSB], [https://www.ebi.ac.uk/pdbsum/3p5j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p5j ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/RNH2A_MOUSE RNH2A_MOUSE]] 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:19923215</ref> [[https://www.uniprot.org/uniprot/RNH2C_MOUSE RNH2C_MOUSE]] 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. [[https://www.uniprot.org/uniprot/RNH2B_MOUSE RNH2B_MOUSE]] 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.
| + | [https://www.uniprot.org/uniprot/RNH2A_MOUSE RNH2A_MOUSE] 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:19923215</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
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| - | The mammalian RNase H2 ribonuclease complex has a critical function in nucleic acid metabolism to prevent immune activation with likely roles in processing of RNA primers in Okazaki fragments during DNA replication, in removing ribonucleotides misinserted by DNA polymerases, and in eliminating RNA.DNA hybrids during cell death. Mammalian RNase H2 is a heterotrimeric complex of the RNase H2A, RNase H2B, and RNase H2C proteins that are all required for proper function and activity. Mutations in the human RNase H2 genes cause Aicardi-Goutieres syndrome. We have determined the crystal structure of the three-protein mouse RNase H2 enzyme complex to better understand the molecular basis of RNase H2 dysfunction in human autoimmunity. The structure reveals the intimately interwoven architecture of RNase H2B and RNase H2C that interface with RNase H2A in a complex ideally suited for nucleic acid binding and hydrolysis coupled to protein-protein interaction motifs that could allow for efficient participation in multiple cellular functions. We have identified four conserved acidic residues in the active site that are necessary for activity and suggest a two-metal ion mechanism of catalysis for RNase H2. An Okazaki fragment has been modeled into the RNase H2 nucleic acid binding site providing insight into the recognition of RNA.DNA junctions by the RNase H2. Further structural and biochemical analyses show that some RNase H2 disease-causing mutations likely result in aberrant protein-protein interactions while the RNase H2A subunit-G37S mutation appears to distort the active site accounting for the demonstrated substrate specificity modification.
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| - | The structure of the mammalian RNase H2 complex provides insight into RNA.NA hybrid processing to prevent immune dysfunction.,Shaban NM, Harvey S, Perrino FW, Hollis T J Biol Chem. 2010 Feb 5;285(6):3617-24. Epub 2009 Nov 18. PMID:19923215<ref>PMID:19923215</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3p5j" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[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]]
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| - | [[Category: Nuclease that cleaves rna/dna hybrid]]
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| - | [[Category: Nucleus]]
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| - | [[Category: Rnase h2 fold]]
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| - | [[Category: Triple beta-barrel]]
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