View source for 8unf


==Cryo-EM structure of T4 Bacteriophage Clamp Loader with Sliding Clamp and DNA==
<StructureSection load='8unf' size='340' side='right'caption='[[8unf]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8unf]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8UNF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UNF 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]] 3.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=08T:[[[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-BIS(OXIDANYL)OXOLAN-2-YL]METHOXY-OXIDANYL-PHOSPHORYL]OXY-OXIDANYL-PHOSPHORYL]OXY-TRIS(FLUORANYL)BERYLLIUM'>08T</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <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=8unf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8unf OCA], [https://pdbe.org/8unf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8unf RCSB], [https://www.ebi.ac.uk/pdbsum/8unf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8unf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CLAMP_BPT4 CLAMP_BPT4] Sliding clamp that encircles the genomic DNA and links the DNA polymerase to the template to control the processivity of DNA synthesis. Responsible for tethering the catalytic subunit of DNA polymerase to DNA during high-speed replication (PubMed:10535942). Interaction with the sliding-clamp-loader opens the sliding clamp so that it can be loaded around the DNA template (PubMed:22194570). During transcription, encircles the DNA and tethers host RNA polymerase (RNAP) to it (PubMed:33602900).[HAMAP-Rule:MF_04161]<ref>PMID:10535942</ref> <ref>PMID:22194570</ref> <ref>PMID:33602900</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Clamp loaders are AAA+ ATPases that facilitate high-speed DNA replication. In eukaryotic and bacteriophage clamp loaders, ATP hydrolysis requires interactions between aspartate residues in one protomer, present in conserved 'DEAD-box' motifs, and arginine residues in adjacent protomers. We show that functional defects resulting from a DEAD-box mutation in the T4 bacteriophage clamp loader can be compensated by widely distributed single mutations in the ATPase domain. Using cryo-EM, we discovered an unsuspected inactive conformation of the clamp loader, in which DNA binding is blocked and the catalytic sites are disassembled. Mutations that restore function map to regions of conformational change upon activation, suggesting that these mutations may increase DNA affinity by altering the energetic balance between inactive and active states. Our results show that there are extensive opportunities for evolution to improve catalytic efficiency when an inactive intermediate is involved.

Autoinhibition of a clamp-loader ATPase revealed by deep mutagenesis and cryo-EM.,Marcus K, Huang Y, Subramanian S, Gee CL, Gorday K, Ghaffari-Kashani S, Luo XR, Zheng L, O'Donnell M, Subramaniam S, Kuriyan J Nat Struct Mol Biol. 2024 Mar;31(3):424-435. doi: 10.1038/s41594-023-01177-3. , Epub 2024 Jan 4. PMID:38177685<ref>PMID:38177685</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8unf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia virus T4]]
[[Category: Large Structures]]
[[Category: Gee LC]]
[[Category: Ghaffari-Kashani S]]
[[Category: Gorday K]]
[[Category: Huang Y]]
[[Category: Kuriyan J]]
[[Category: Luo X]]
[[Category: Marcus K]]
[[Category: O'Donnell M]]
[[Category: Subramanian S]]
[[Category: Zhang L]]