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7kiu

From Proteopedia

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Current revision

Structure of recombinant human DNase1L3 in complex with Mg2+

Structural highlights

7kiu 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.
Method:	X-ray diffraction, Resolution 2.22Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

DNSL3_HUMAN Autosomal systemic lupus erythematosus;Hypocomplementemic urticarial vasculitis. The disease is caused by variants affecting the gene represented in this entry.

Function

DNSL3_HUMAN Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends (By similarity). Can cleave chromatin to nucleosomal units and cleaves nucleosomal and liposome-coated DNA (PubMed:9070308, PubMed:9714828, PubMed:14646506, PubMed:10807908, PubMed:27293190). Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis (PubMed:23229555, PubMed:24312463). The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells (By similarity). Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (PubMed:27293190). Together with DNASE1, plays a key role in degrading neutrophil extracellular traps (NETs) (By similarity). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (By similarity).[UniProtKB:O55070][UniProtKB:O89107]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

Autoimmunity develops when extracellular DNA released from dying cells is not cleared from serum. While serum DNA is primarily digested by Dnase1 and Dnase1L3, Dnase1 cannot rescue autoimmunity arising from Dnase1L3 deficiencies. Dnase1L3 uniquely degrades antigenic forms of cell-free DNA, including DNA complexed with lipids and proteins. The distinct activity of Dnase1L3 relies on its unique C-terminal Domain (CTD), but the mechanism is unknown. We used multiple biophysical techniques and functional assays to study the interplay between the core catalytic domain and the CTD. While the core domain resembles Dnase1, there are key structural differences between the two enzymes. First, Dnase1L3 is not inhibited by actin due to multiple differences in the actin recognition site. Second, the CTD augments the ability of the core to bind DNA, thereby facilitating the degradation of complexed DNA. Together, these structural insights will inform the development of Dnase1L3-based therapies for autoimmunity.

Structural features of Dnase1L3 responsible for serum antigen clearance.,McCord JJ, Engavale M, Masoumzadeh E, Villarreal J, Mapp B, Latham MP, Keyel PA, Sutton RB Commun Biol. 2022 Aug 16;5(1):825. doi: 10.1038/s42003-022-03755-5. PMID:35974043^[8]

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

References

↑ Yakovlev AG, Wang G, Stoica BA, Boulares HA, Spoonde AY, Yoshihara K, Smulson ME. A role of the Ca2+/Mg2+-dependent endonuclease in apoptosis and its inhibition by Poly(ADP-ribose) polymerase. J Biol Chem. 2000 Jul 14;275(28):21302-8. doi: 10.1074/jbc.M001087200. PMID:10807908 doi:http://dx.doi.org/10.1074/jbc.M001087200
↑ Shiokawa D, Hirai M, Tanuma S. cDNA cloning of human DNase gamma: chromosomal localization of its gene and enzymatic properties of recombinant protein. Apoptosis. 1998 Mar;3(2):89-95. doi: 10.1023/a:1009692807692. PMID:14646506 doi:http://dx.doi.org/10.1023/a:1009692807692
↑ Errami Y, Naura AS, Kim H, Ju J, Suzuki Y, El-Bahrawy AH, Ghonim MA, Hemeida RA, Mansy MS, Zhang J, Xu M, Smulson ME, Brim H, Boulares AH. Apoptotic DNA fragmentation may be a cooperative activity between caspase-activated deoxyribonuclease and the poly(ADP-ribose) polymerase-regulated DNAS1L3, an endoplasmic reticulum-localized endonuclease that translocates to the nucleus during apoptosis. J Biol Chem. 2013 Feb 1;288(5):3460-8. doi: 10.1074/jbc.M112.423061. Epub 2012, Dec 10. PMID:23229555 doi:http://dx.doi.org/10.1074/jbc.M112.423061
↑ Mizuta R, Araki S, Furukawa M, Furukawa Y, Ebara S, Shiokawa D, Hayashi K, Tanuma S, Kitamura D. DNase gamma is the effector endonuclease for internucleosomal DNA fragmentation in necrosis. PLoS One. 2013 Dec 2;8(12):e80223. doi: 10.1371/journal.pone.0080223. eCollection, 2013. PMID:24312463 doi:http://dx.doi.org/10.1371/journal.pone.0080223
↑ Sisirak V, Sally B, D'Agati V, Martinez-Ortiz W, Ozcakar ZB, David J, Rashidfarrokhi A, Yeste A, Panea C, Chida AS, Bogunovic M, Ivanov II, Quintana FJ, Sanz I, Elkon KB, Tekin M, Yalcinkaya F, Cardozo TJ, Clancy RM, Buyon JP, Reizis B. Digestion of Chromatin in Apoptotic Cell Microparticles Prevents Autoimmunity. Cell. 2016 Jun 30;166(1):88-101. doi: 10.1016/j.cell.2016.05.034. Epub 2016 Jun, 9. PMID:27293190 doi:http://dx.doi.org/10.1016/j.cell.2016.05.034
↑ Zeng Z, Parmelee D, Hyaw H, Coleman TA, Su K, Zhang J, Gentz R, Ruben S, Rosen C, Li Y. Cloning and characterization of a novel human DNase. Biochem Biophys Res Commun. 1997 Feb 13;231(2):499-504. doi:, 10.1006/bbrc.1996.5923. PMID:9070308 doi:http://dx.doi.org/10.1006/bbrc.1996.5923
↑ Baron WF, Pan CQ, Spencer SA, Ryan AM, Lazarus RA, Baker KP. Cloning and characterization of an actin-resistant DNase I-like endonuclease secreted by macrophages. Gene. 1998 Jul 30;215(2):291-301. doi: 10.1016/s0378-1119(98)00281-9. PMID:9714828 doi:http://dx.doi.org/10.1016/s0378-1119(98)00281-9
↑ McCord JJ, Engavale M, Masoumzadeh E, Villarreal J, Mapp B, Latham MP, Keyel PA, Sutton RB. Structural features of Dnase1L3 responsible for serum antigen clearance. Commun Biol. 2022 Aug 16;5(1):825. doi: 10.1038/s42003-022-03755-5. PMID:35974043 doi:http://dx.doi.org/10.1038/s42003-022-03755-5

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/7kiu"

Categories: Homo sapiens | Large Structures | Keyel PA | McCord JJ | Sutton RB

@@ Line 3: / Line 3: @@
 <StructureSection load='7kiu' size='340' side='right'caption='[[7kiu]], [[Resolution|resolution]] 2.22&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7kiu]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KIU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7kiu]] 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=7KIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KIU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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]] 2.22&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7kiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kiu OCA], [https://pdbe.org/7kiu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kiu RCSB], [https://www.ebi.ac.uk/pdbsum/7kiu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kiu ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/DNSL3_HUMAN DNSL3_HUMAN]] Autosomal systemic lupus erythematosus;Hypocomplementemic urticarial vasculitis. The disease is caused by variants affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/DNSL3_HUMAN DNSL3_HUMAN] Autosomal systemic lupus erythematosus;Hypocomplementemic urticarial vasculitis. The disease is caused by variants affecting the gene represented in this entry.
 == Function ==
-[[https://www.uniprot.org/uniprot/DNSL3_HUMAN DNSL3_HUMAN]] Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends (By similarity). Can cleave chromatin to nucleosomal units and cleaves nucleosomal and liposome-coated DNA (PubMed:9070308, PubMed:9714828, PubMed:14646506, PubMed:10807908, PubMed:27293190). Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis (PubMed:23229555, PubMed:24312463). The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells (By similarity). Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (PubMed:27293190). Together with DNASE1, plays a key role in degrading neutrophil extracellular traps (NETs) (By similarity). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (By similarity).[UniProtKB:O55070][UniProtKB:O89107]<ref>PMID:10807908</ref> <ref>PMID:14646506</ref> <ref>PMID:23229555</ref> <ref>PMID:24312463</ref> <ref>PMID:27293190</ref> <ref>PMID:9070308</ref> <ref>PMID:9714828</ref>
+[https://www.uniprot.org/uniprot/DNSL3_HUMAN DNSL3_HUMAN] Has DNA hydrolytic activity. Is capable of both single- and double-stranded DNA cleavage, producing DNA fragments with 3'-OH ends (By similarity). Can cleave chromatin to nucleosomal units and cleaves nucleosomal and liposome-coated DNA (PubMed:9070308, PubMed:9714828, PubMed:14646506, PubMed:10807908, PubMed:27293190). Acts in internucleosomal DNA fragmentation (INDF) during apoptosis and necrosis (PubMed:23229555, PubMed:24312463). The role in apoptosis includes myogenic and neuronal differentiation, and BCR-mediated clonal deletion of self-reactive B cells (By similarity). Is active on chromatin in apoptotic cell-derived membrane-coated microparticles and thus suppresses anti-DNA autoimmunity (PubMed:27293190). Together with DNASE1, plays a key role in degrading neutrophil extracellular traps (NETs) (By similarity). NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Degradation of intravascular NETs by DNASE1 and DNASE1L3 is required to prevent formation of clots that obstruct blood vessels and cause organ damage following inflammation (By similarity).[UniProtKB:O55070][UniProtKB:O89107]<ref>PMID:10807908</ref> <ref>PMID:14646506</ref> <ref>PMID:23229555</ref> <ref>PMID:24312463</ref> <ref>PMID:27293190</ref> <ref>PMID:9070308</ref> <ref>PMID:9714828</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Keyel, P A]]
+[[Category: Keyel PA]]
-[[Category: McCord, J J]]
+[[Category: McCord JJ]]
-[[Category: Sutton, R B]]
+[[Category: Sutton RB]]
-[[Category: Apoptosis]]
-[[Category: Dna clearance]]
-[[Category: Dna hydrolase]]
-[[Category: Hydrolase]]
-[[Category: Lupus]]
-[[Category: Metal ion nuclease]]
-[[Category: Net clearance]]
-[[Category: Nuclease]]
-[[Category: Sle]]
-[[Category: Systemic lupus erythematosus]]

7kiu

From Proteopedia

Current revision

Structure of recombinant human DNase1L3 in complex with Mg2+

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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