7nfc: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-====
+==Cryo-EM structure of NHEJ super-complex (dimer)==
-<StructureSection load='7nfc' size='340' side='right'caption='[[7nfc]]' scene=''>
+<StructureSection load='7nfc' size='340' side='right'caption='[[7nfc]], [[Resolution|resolution]] 4.14&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7nfc]] is a 18 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=7NFC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NFC FirstGlance]. <br>
-</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=7nfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nfc OCA], [https://pdbe.org/7nfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nfc RCSB], [https://www.ebi.ac.uk/pdbsum/7nfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nfc ProSAT]</span></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]] 4.14&#8491;</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=7nfc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nfc OCA], [https://pdbe.org/7nfc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nfc RCSB], [https://www.ebi.ac.uk/pdbsum/7nfc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nfc ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PRKDC_HUMAN PRKDC_HUMAN] Severe combined immunodeficiency due to DNA-PKcs deficiency. The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/PRKDC_HUMAN PRKDC_HUMAN] Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Required to protect and align broken ends of DNA. May also act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. Also involved in modulation of transcription. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX, thereby regulating DNA damage response mechanism. Phosphorylates DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, SRF, XRCC1, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2. Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA. Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D. Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect machanism. Interacts with CRY1 and CRY2; negatively regulates CRY1 phosphorylation.<ref>PMID:12649176</ref> <ref>PMID:14734805</ref> <ref>PMID:15574326</ref> <ref>PMID:9679063</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Non-homologous end joining (NHEJ) is one of two critical mechanisms utilized in humans to repair DNA double-strand breaks (DSBs). Unrepaired or incorrect repair of DSBs can lead to apoptosis or cancer. NHEJ involves several proteins, including the Ku70/80 heterodimer, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), X-ray cross-complementing protein 4 (XRCC4), XRCC4-like factor (XLF), and ligase IV. These core proteins bind DSBs and ligate the damaged DNA ends. However, details of the structural assembly of these proteins remain unclear. Here, we present cryo-EM structures of NHEJ supercomplexes that are composed of these core proteins and DNA, revealing the detailed structural architecture of this assembly. We describe monomeric and dimeric forms of this supercomplex and also propose the existence of alternate dimeric forms of long-range synaptic complexes. Finally, we show that mutational disruption of several structural features within these NHEJ complexes negatively affects DNA repair.
+Cryo-EM of NHEJ supercomplexes provides insights into DNA repair.,Chaplin AK, Hardwick SW, Stavridi AK, Buehl CJ, Goff NJ, Ropars V, Liang S, De Oliveira TM, Chirgadze DY, Meek K, Charbonnier JB, Blundell TL Mol Cell. 2021 Aug 19;81(16):3400-3409.e3. doi: 10.1016/j.molcel.2021.07.005. , Epub 2021 Aug 4. PMID:34352203<ref>PMID:34352203</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7nfc" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA ligase 3D structures|DNA ligase 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Z-disk]]
+[[Category: Blundell TL]]
+[[Category: Chaplin AK]]
+[[Category: Chirgadze DY]]
+[[Category: Hardwick SW]]
+[[Category: Kefala Stavridi A]]