6di2: Difference between revisions
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==Crystal structure of eukaryotic DNA primase large subunit iron-sulfur cluster domain Y397L mutant== | |||
<StructureSection load='6di2' size='340' side='right'caption='[[6di2]], [[Resolution|resolution]] 1.32Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6di2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_JAY291 Saccharomyces cerevisiae JAY291]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DI2 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.32Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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=6di2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6di2 OCA], [https://pdbe.org/6di2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6di2 RCSB], [https://www.ebi.ac.uk/pdbsum/6di2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6di2 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/C7GP29_YEAS2 C7GP29_YEAS2] DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication.[PIRNR:PIRNR009449] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Eukaryotic DNA primases contain a [4Fe4S] cluster in the C-terminal domain of the p58 subunit (p58C) that affects substrate affinity but is not required for catalysis. We show that, in yeast primase, the cluster serves as a DNA-mediated redox switch governing DNA binding, just as in human primase. Despite a different structural arrangement of tyrosines to facilitate electron transfer between the DNA substrate and [4Fe4S] cluster, in yeast, mutation of tyrosines Y395 and Y397 alters the same electron transfer chemistry and redox switch. Mutation of conserved tyrosine 395 diminishes the extent of p58C participation in normal redox-switching reactions, whereas mutation of conserved tyrosine 397 causes oxidative cluster degradation to the [3Fe4S](+) species during p58C redox signaling. Switching between oxidized and reduced states in the presence of the Y397 mutations thus puts primase [4Fe4S] cluster integrity and function at risk. Consistent with these observations, we find that yeast tolerate mutations to Y395 in p58C, but the single-residue mutation Y397L in p58C is lethal. Our data thus show that a constellation of tyrosines for protein-DNA electron transfer mediates the redox switch in eukaryotic primases and is required for primase function in vivo. | |||
Yeast require redox switching in DNA primase.,O'Brien E, Salay LE, Epum EA, Friedman KL, Chazin WJ, Barton JK Proc Natl Acad Sci U S A. 2018 Dec 12. pii: 1810715115. doi:, 10.1073/pnas.1810715115. PMID:30541886<ref>PMID:30541886</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Chazin | <div class="pdbe-citations 6di2" style="background-color:#fffaf0;"></div> | ||
[[Category: Salay | |||
==See Also== | |||
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae JAY291]] | |||
[[Category: Chazin WJ]] | |||
[[Category: Salay LE]] | |||