8rwv
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Human OCCM DNA licensing intermediate== |
| + | <StructureSection load='8rwv' size='340' side='right'caption='[[8rwv]], [[Resolution|resolution]] 6.68Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8rwv]] is a 10 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=8RWV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8RWV FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6.68Å</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=8rwv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8rwv OCA], [https://pdbe.org/8rwv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8rwv RCSB], [https://www.ebi.ac.uk/pdbsum/8rwv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8rwv ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/MCM4_HUMAN MCM4_HUMAN] Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MCM4_HUMAN MCM4_HUMAN] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.<ref>PMID:16899510</ref> <ref>PMID:9305914</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human DNA licensing initiates replication fork assembly and DNA replication. This reaction promotes the loading of the hMCM2-7 complex on DNA, which represents the core of the replicative helicase that unwinds DNA during S-phase. Here, we report the reconstitution of human DNA licensing using purified proteins. We showed that the in vitro reaction is specific and results in the assembly of high-salt resistant hMCM2-7 double-hexamers. With ATPgammaS, an hORC1-5-hCDC6-hCDT1-hMCM2-7 (hOCCM) assembles independent of hORC6, but hORC6 enhances double-hexamer formation. We determined the hOCCM structure, which showed that hORC-hCDC6 recruits hMCM2-7 via five hMCM winged-helix domains. The structure highlights how hORC1 activates the hCDC6 ATPase and uncovered an unexpected role for hCDC6 ATPase in complex disassembly. We identified that hCDC6 binding to hORC1-5 stabilises hORC2-DNA interactions and supports hMCM3-dependent recruitment of hMCM2-7. Finally, the structure allowed us to locate cancer-associated mutations at the hCDC6-hMCM3 interface, which showed specific helicase loading defects. | ||
| - | + | Reconstitution of human DNA licensing and the structural and functional analysis of key intermediates.,Wells JN, Edwardes LV, Leber V, Allyjaun S, Peach M, Tomkins J, Kefala-Stavridi A, Faull SV, Aramayo R, Pestana CM, Ranjha L, Speck C Nat Commun. 2025 Jan 8;16(1):478. doi: 10.1038/s41467-024-55772-z. PMID:39779677<ref>PMID:39779677</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8rwv" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Allyjaun S]] | ||
| + | [[Category: Aramayo R]] | ||
| + | [[Category: Edwards LV]] | ||
| + | [[Category: Faull SV]] | ||
| + | [[Category: Kefala-Stavridi A]] | ||
| + | [[Category: Leber V]] | ||
| + | [[Category: Peach M]] | ||
| + | [[Category: Pestana CM]] | ||
| + | [[Category: Ranjha L]] | ||
| + | [[Category: Speck C]] | ||
| + | [[Category: Tomkins J]] | ||
| + | [[Category: Wells JN]] | ||
Current revision
Human OCCM DNA licensing intermediate
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Categories: Homo sapiens | Large Structures | Allyjaun S | Aramayo R | Edwards LV | Faull SV | Kefala-Stavridi A | Leber V | Peach M | Pestana CM | Ranjha L | Speck C | Tomkins J | Wells JN
