2V0S: Crystal Structure Of A Hairpin Exchange Variant (Lr1) Of The Targeting Line-1 Retrotransposon Endonuclease

Citation:
Abstract
The human LINE-1 endonuclease (L1-EN) is the targeting endonuclease encoded by the human LINE-1 (L1) retrotransposon. L1-EN guides the genomic integration of new L1 and Alu elements that presently account for approximately 28% of the human genome. L1-EN bears considerable technological interest, because its target selectivity may ultimately be engineered to allow the site-specific integration of DNA into defined genomic locations. Based on the crystal structure, we generated L1-EN mutants to analyze and manipulate DNA target site recognition. Crystal structures and their dynamic and functional analysis show entire loop grafts to be feasible, resulting in altered specificity, while individual point mutations do not change the nicking pattern of L1-EN. Structural parameters of the DNA target seem more important for recognition than the nucleotide sequence, and nicking profiles on DNA oligonucleotides in vitro are less well defined than the respective integration site consensus in vivo. This suggests that additional factors other than the DNA nicking specificity of L1-EN contribute to the targeted integration of non-LTR retrotransposons.
PDB ID: 2V0SDownload
MMDB ID: 47561
PDB Deposition Date: 2007/5/17
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 2V0S: monomeric; determined by author and by software (PQS)
Molecular Components in 2V0S
Label Count Molecule
Protein (1 molecule)
1
LR1
Molecule annotation
Chemicals (4 molecules)
1
1
2
2
3
1
* Click molecule labels to explore molecular sequence information.

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