title: DNA binding induces active site conformational change in the human TREX2 3'-exonuclease.
abstract: The TREX enzymes process DNA as the major 3'-->5' exonuclease activity in mammalian cells. TREX2 and TREX1 are members of the DnaQ family of exonucleases and utilize a two metal ion catalytic mechanism of hydrolysis. The structure of the dimeric TREX2 enzyme in complex with single-stranded DNA has revealed binding properties that are distinct from the TREX1 protein. The TREX2 protein undergoes a conformational change in the active site upon DNA binding including ordering of active site residues and a shift of an active site helix. Surprisingly, even when a single monomer binds DNA, both monomers in the dimer undergo the structural rearrangement. From this we have proposed a model for DNA binding and 3' hydrolysis for the TREX2 dimer. The structure also shows how TREX proteins potentially interact with double-stranded DNA and suggest features that might be involved in strand denaturation to provide a single-stranded substrate for the active site.
authors.affiliation: Department of Biochemistry, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
authors.forename: Udesh
authors.initials: U
authors.lastname: de Silva
authors.forename: Fred W
authors.initials: FW
authors.lastname: Perrino
authors.forename: Thomas
authors.initials: T
authors.lastname: Hollis