Crystal structure of the targeting endonuclease of the human LINE-1 retrotransposon.
The human L1 endonuclease (L1-EN) is encoded by the non-LTR retrotransposon LINE-1 (L1). L1 is responsible for more than 1.5 million retrotransposition events in the history of the human genome, contributing more than a quarter to human genomic DNA (L1 and Alu elements). L1-EN is related to the well-understood human DNA repair endonuclease APE1, and its nicking specificity is a major determinant for retrotransposon integration site selection. The crystal structure of human L1 endonuclease is the first of a retrotransposon-encoded protein and a prototype for retrotransposon-encoded endonucleases involved in target-primed reverse transcription. Structure-based endonuclease alignments reveal a conserved threonine in addition to previously identified invariant residues and suggest that DNA recognition proceeds via the accommodation of an extrahelical nucleotide within a pocket of the enzyme. The present analysis will help to refine phylogenetic and functional relationships among metal-dependent phosphohydrolases and provides a basis for manipulating non-LTR retrotransposon integration site selection.
Weichenrieder
Oliver
O
The Netherlands Cancer Institute, Department of Molecular Carcinogenesis-H2, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. o.weichenrieder@nki.nl
Repanas
Kostas
K
Perrakis
Anastassis
A
D000595:Amino Acid Sequence; D001665:Binding Sites; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray / Q000379:methods*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004260:DNA Repair; D019992:Databases as Topic; D004720:Endonucleases / Q000737:chemistry*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry; D010802:Phylogeny; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D018626:Retroelements / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D011994:Recombinant Proteins; D018626:Retroelements; D004247:DNA; D004720:Endonucleases; C488774:endonuclease L1, human; D010744:Phosphoric Monoester Hydrolases