6a45 | pdb_00006a45

Structure of mouse TREX2

spinqualitylabelsall models 6a45, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6a45 is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: PO4 Gene: Trex2 (LK3 transgenic mice) Activity: Exodeoxyribonuclease III, with EC number 3.1.11.2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The three prime repair exonuclease 2 (TREX2) is an essential 3'-to-5' exonuclease that functions in cell proliferation, genome integrity and skin homeostasis maintenance. The abnormal expression level of TREX2 can result in broken chromosome, increased susceptibility to skin carcinogenesis and Psoriasis. However, the molecular mechanisms of how TREX2 binds and processes its natural substrates, dsDNA or chromosomal DNA, to maintain genome stability remain unclear. In this study, we present four new crystal structures: apo-TREX2, TREX2 in complex with two different dsDNA substrates, and TREX2 in complex with a processed dsDNA product. Analysis of the structures reveals that TREX2 stacks with the 5'-terminal of dsDNA by a Leu20-Pro21-Asn22 cluster for precisely trimming the 3'-overhang. In addition, TREX2 specifically interacts with the non-scissile strand of dsDNA by an alpha-helix-loop region. The unique interaction patterns of the TREX2-dsDNA complex highlight the requirement of long double-stranded region for TREX2 binding and provide evidence of the functional role of TREX2 in processing chromosomal DNA. Moreover, the non-processive property of TREX2 is elucidated by the structure of TREX2-product complex. Our work discloses the first structural basis of the molecular interactions between TREX2 and its substrates and unravels the mechanistic actions of TREX2. Structural insights into the duplex DNA processing of TREX2.,Cheng HL, Lin CT, Huang KW, Wang S, Lin YT, Toh SI, Hsiao YY Nucleic Acids Res. 2018 Oct 24. pii: 5144137. doi: 10.1093/nar/gky970. PMID:30357414 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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