5np7

From Proteopedia

(Difference between revisions)

Current revision

CryoEM structure of Human Rad51 on single-stranded DNA to 4.2A resolution.

5np7, resolution 4.20Å

Structural highlights

5np7 is a 7 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:	Electron Microscopy, Resolution 4.2Å
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

RAD51_HUMAN Defects in RAD51 are a cause of susceptibility to breast cancer (BC) [MIM:114480. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.^[1] Defects in RAD51 are the cause of mirror movements type 2 (MRMV2) [MIM:614508. A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities.^[2]

Function

RAD51_HUMAN Participates in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Binds to single and double stranded DNA and exhibits DNA-dependent ATPase activity. Underwinds duplex DNA and forms helical nucleoprotein filaments. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3.^[3] ^[4] ^[5]

Publication Abstract from PubMed

Homologous DNA recombination (HR) by the RAD51 recombinase enables error-free DNA break repair. To execute HR, RAD51 first forms a presynaptic filament on single-stranded (ss) DNA, which catalyses pairing with homologous double-stranded (ds) DNA. Here, we report a structure for the presynaptic human RAD51 filament at 3.5-5.0A resolution using electron cryo-microscopy. RAD51 encases ssDNA in a helical filament of 103A pitch, comprising 6.4 protomers per turn, with a rise of 16.1A and a twist of 56.2 degrees . Inter-protomer distance correlates with rotation of an alpha-helical region in the core catalytic domain that is juxtaposed to ssDNA, suggesting how the RAD51-DNA interaction modulates protomer spacing and filament pitch. We map Fanconi anaemia-like disease-associated RAD51 mutations, clarifying potential phenotypes. We predict binding sites on the presynaptic filament for two modules present in each BRC repeat of the BRCA2 tumour suppressor, a critical HR mediator. Structural modelling suggests that changes in filament pitch mask or expose one binding site with filament-inhibitory potential, rationalizing the paradoxical ability of the BRC repeats to either stabilize or inhibit filament formation at different steps during HR. Collectively, our findings provide fresh insight into the structural mechanism of HR and its dysregulation in human disease.

High-resolution structure of the presynaptic RAD51 filament on single-stranded DNA by electron cryo-microscopy.,Short JM, Liu Y, Chen S, Soni N, Madhusudhan MS, Shivji MK, Venkitaraman AR Nucleic Acids Res. 2016 Sep 5. pii: gkw783. PMID:27596592^[6]

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

References

↑ Kato M, Yano K, Matsuo F, Saito H, Katagiri T, Kurumizaka H, Yoshimoto M, Kasumi F, Akiyama F, Sakamoto G, Nagawa H, Nakamura Y, Miki Y. Identification of Rad51 alteration in patients with bilateral breast cancer. J Hum Genet. 2000;45(3):133-7. PMID:10807537 doi:10.1007/s100380050199
↑ Depienne C, Bouteiller D, Meneret A, Billot S, Groppa S, Klebe S, Charbonnier-Beaupel F, Corvol JC, Saraiva JP, Brueggemann N, Bhatia K, Cincotta M, Brochard V, Flamand-Roze C, Carpentier W, Meunier S, Marie Y, Gaussen M, Stevanin G, Wehrle R, Vidailhet M, Klein C, Dusart I, Brice A, Roze E. RAD51 haploinsufficiency causes congenital mirror movements in humans. Am J Hum Genet. 2012 Feb 10;90(2):301-7. doi: 10.1016/j.ajhg.2011.12.002. Epub, 2012 Feb 2. PMID:22305526 doi:10.1016/j.ajhg.2011.12.002
↑ Park JY, Yoo HW, Kim BR, Park R, Choi SY, Kim Y. Identification of a novel human Rad51 variant that promotes DNA strand exchange. Nucleic Acids Res. 2008 Jun;36(10):3226-34. doi: 10.1093/nar/gkn171. Epub 2008, Apr 16. PMID:18417535 doi:10.1093/nar/gkn171
↑ Sigurdsson S, Van Komen S, Petukhova G, Sung P. Homologous DNA pairing by human recombination factors Rad51 and Rad54. J Biol Chem. 2002 Nov 8;277(45):42790-4. Epub 2002 Aug 29. PMID:12205100 doi:10.1074/jbc.M208004200
↑ Sage JM, Gildemeister OS, Knight KL. Discovery of a novel function for human Rad51: maintenance of the mitochondrial genome. J Biol Chem. 2010 Jun 18;285(25):18984-90. doi: 10.1074/jbc.M109.099846. Epub, 2010 Apr 22. PMID:20413593 doi:10.1074/jbc.M109.099846
↑ Short JM, Liu Y, Chen S, Soni N, Madhusudhan MS, Shivji MK, Venkitaraman AR. High-resolution structure of the presynaptic RAD51 filament on single-stranded DNA by electron cryo-microscopy. Nucleic Acids Res. 2016 Sep 5. pii: gkw783. PMID:27596592 doi:http://dx.doi.org/10.1093/nar/gkw783

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/5np7"

Categories: Homo sapiens | Large Structures | Short JM | Venkitaraman A

@@ Line 3: / Line 3: @@
 <SX load='5np7' size='340' side='right' viewer='molstar' caption='[[5np7]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5np7]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NP7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NP7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5np7]] is a 7 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=5NP7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NP7 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.2&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RAD51, RAD51A, RECA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5np7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5np7 OCA], [http://pdbe.org/5np7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5np7 RCSB], [http://www.ebi.ac.uk/pdbsum/5np7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5np7 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=5np7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5np7 OCA], [https://pdbe.org/5np7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5np7 RCSB], [https://www.ebi.ac.uk/pdbsum/5np7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5np7 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/RAD51_HUMAN RAD51_HUMAN]] Defects in RAD51 are a cause of susceptibility to breast cancer (BC) [MIM:[http://omim.org/entry/114480 114480]]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.<ref>PMID:10807537</ref>   Defects in RAD51 are the cause of mirror movements type 2 (MRMV2) [MIM:[http://omim.org/entry/614508 614508]]. A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities.<ref>PMID:22305526</ref>
+[https://www.uniprot.org/uniprot/RAD51_HUMAN RAD51_HUMAN] Defects in RAD51 are a cause of susceptibility to breast cancer (BC) [MIM:[https://omim.org/entry/114480 114480]. A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.<ref>PMID:10807537</ref>   Defects in RAD51 are the cause of mirror movements type 2 (MRMV2) [MIM:[https://omim.org/entry/614508 614508]. A disorder characterized by contralateral involuntary movements that mirror voluntary ones. While mirror movements are occasionally found in young children, persistence beyond the age of 10 is abnormal. Mirror movements occur more commonly in the upper extremities.<ref>PMID:22305526</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/RAD51_HUMAN RAD51_HUMAN]] Participates in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Binds to single and double stranded DNA and exhibits DNA-dependent ATPase activity. Underwinds duplex DNA and forms helical nucleoprotein filaments. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3.<ref>PMID:18417535</ref> <ref>PMID:12205100</ref> <ref>PMID:20413593</ref>
+[https://www.uniprot.org/uniprot/RAD51_HUMAN RAD51_HUMAN] Participates in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Binds to single and double stranded DNA and exhibits DNA-dependent ATPase activity. Underwinds duplex DNA and forms helical nucleoprotein filaments. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3.<ref>PMID:18417535</ref> <ref>PMID:12205100</ref> <ref>PMID:20413593</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 __TOC__
 </SX>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Short, J M]]
+[[Category: Short JM]]
-[[Category: Venkitaraman, A]]
+[[Category: Venkitaraman A]]
-[[Category: Cryoem]]
-[[Category: Human rad51]]
-[[Category: Recombinase]]
-[[Category: Recombination]]
-[[Category: Single-stranded dna]]

5np7

From Proteopedia

Current revision

CryoEM structure of Human Rad51 on single-stranded DNA to 4.2A resolution.

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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