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6WWA

Crystal structure of human SHLD2-SHLD3-REV7 complex

Summary for 6WWA
Entry DOI10.2210/pdb6wwa/pdb
DescriptorMitotic spindle assembly checkpoint protein MAD2B, Shieldin complex subunit 2,Shieldin complex subunit 3 chimera (2 entities in total)
Functional Keywordsrev7, shld2, shld3, nuclear protein
Biological sourceHomo sapiens (Human)
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Total number of polymer chains6
Total formula weight118649.67
Authors
Xie, W.,Patel, D.J. (deposition date: 2020-05-08, release date: 2021-03-03, Last modification date: 2023-10-18)
Primary citationXie, W.,Wang, S.,Wang, J.,de la Cruz, M.J.,Xu, G.,Scaltriti, M.,Patel, D.J.
Molecular mechanisms of assembly and TRIP13-mediated remodeling of the human Shieldin complex.
Proc.Natl.Acad.Sci.USA, 118:-, 2021
Cited by
PubMed Abstract: The Shieldin complex, composed of REV7, SHLD1, SHLD2, and SHLD3, protects DNA double-strand breaks (DSBs) to promote nonhomologous end joining. The AAA ATPase TRIP13 remodels Shieldin to regulate DNA repair pathway choice. Here we report crystal structures of human SHLD3-REV7 binary and fused SHLD2-SHLD3-REV7 ternary complexes, revealing that assembly of Shieldin requires fused SHLD2-SHLD3 induced conformational heterodimerization of open (O-REV7) and closed (C-REV7) forms of REV7. We also report the cryogenic electron microscopy (cryo-EM) structures of the ATPγS-bound fused SHLD2-SHLD3-REV7-TRIP13 complexes, uncovering the principles underlying the TRIP13-mediated disassembly mechanism of the Shieldin complex. We demonstrate that the N terminus of REV7 inserts into the central channel of TRIP13, setting the stage for pulling the unfolded N-terminal peptide of C-REV7 through the central TRIP13 hexameric channel. The primary interface involves contacts between the safety-belt segment of C-REV7 and a conserved and negatively charged loop of TRIP13. This process is mediated by ATP hydrolysis-triggered rotatory motions of the TRIP13 ATPase, thereby resulting in the disassembly of the Shieldin complex.
PubMed: 33597306
DOI: 10.1073/pnas.2024512118
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (3.8 Å)
Structure validation

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