5da9

From Proteopedia

(Difference between revisions)

Current revision

ATP-gamma-S bound Rad50 from Chaetomium thermophilum in complex with the Rad50-binding domain of Mre11

Structural highlights

5da9 is a 4 chain structure with sequence from Chaetomium thermophilum var. thermophilum DSM 1495. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RAD50_CHATD Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (By similarity). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (By similarity). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (By similarity). The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (By similarity). Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11 (PubMed:26896444, PubMed:36577401). RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form (PubMed:36577401).[UniProtKB:Q92878]^[1] ^[2]

Publication Abstract from PubMed

The Mre11-Rad50-Nbs1 (MRN) complex is a central factor in the repair of DNA double-strand breaks (DSBs). The ATP-dependent mechanisms of how MRN detects and endonucleolytically processes DNA ends for the repair by microhomology-mediated end-joining or further resection in homologous recombination are still unclear. Here, we report the crystal structures of the ATPgammaS-bound dimer of the Rad50NBD (nucleotide-binding domain) from the thermophilic eukaryote Chaetomium thermophilum (Ct) in complex with either DNA or CtMre11RBD (Rad50-binding domain) along with small-angle X-ray scattering and cross-linking studies. The structure and DNA binding motifs were validated by DNA binding experiments in vitro and mutational analyses in Saccharomyces cerevisiae in vivo. Our analyses provide a structural framework for the architecture of the eukaryotic Mre11-Rad50 complex. They show that a Rad50 dimer binds approximately 18 base pairs of DNA along the dimer interface in an ATP-dependent fashion or bridges two DNA ends with a preference for 3' overhangs. Finally, our results may provide a general framework for the interaction of ABC ATPase domains of the Rad50/SMC/RecN protein family with DNA.

Structural mechanism of ATP-dependent DNA binding and DNA end bridging by eukaryotic Rad50.,Seifert FU, Lammens K, Stoehr G, Kessler B, Hopfner KP EMBO J. 2016 Feb 19. pii: e201592934. PMID:26896444^[3]

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

References

↑ Seifert FU, Lammens K, Stoehr G, Kessler B, Hopfner KP. Structural mechanism of ATP-dependent DNA binding and DNA end bridging by eukaryotic Rad50. EMBO J. 2016 Feb 19. pii: e201592934. PMID:26896444 doi:http://dx.doi.org/10.15252/embj.201592934
↑ Rotheneder M, Stakyte K, van de Logt E, Bartho JD, Lammens K, Fan Y, Alt A, Kessler B, Jung C, Roos WP, Steigenberger B, Hopfner KP. Cryo-EM structure of the Mre11-Rad50-Nbs1 complex reveals the molecular mechanism of scaffolding functions. Mol Cell. 2022 Dec 20:S1097-2765(22)01138-8. doi: 10.1016/j.molcel.2022.12.003. PMID:36577401 doi:http://dx.doi.org/10.1016/j.molcel.2022.12.003
↑ Seifert FU, Lammens K, Stoehr G, Kessler B, Hopfner KP. Structural mechanism of ATP-dependent DNA binding and DNA end bridging by eukaryotic Rad50. EMBO J. 2016 Feb 19. pii: e201592934. PMID:26896444 doi:http://dx.doi.org/10.15252/embj.201592934

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5da9"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5da9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum_var._thermophilum_DSM_1495 Chaetomium thermophilum var. thermophilum DSM 1495]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DA9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DA9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=5da9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5da9 OCA], [https://pdbe.org/5da9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5da9 RCSB], [https://www.ebi.ac.uk/pdbsum/5da9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5da9 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/G0SHW7_CHATD G0SHW7_CHATD]
+[https://www.uniprot.org/uniprot/RAD50_CHATD RAD50_CHATD] Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (By similarity). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (By similarity). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (By similarity). The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (By similarity). Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11 (PubMed:26896444, PubMed:36577401). RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form (PubMed:36577401).[UniProtKB:Q92878]<ref>PMID:26896444</ref> <ref>PMID:36577401</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

5da9

From Proteopedia

Current revision

ATP-gamma-S bound Rad50 from Chaetomium thermophilum in complex with the Rad50-binding domain of Mre11

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox