Structures, functions and adaptations of the human LINE-1 ORF2 protein.

ABSTRACT: The LINE-1 (L1) retrotransposon is an ancient genetic parasite that has written around one-third of the human genome through a 'copy and paste' mechanism catalysed by its multifunctional enzyme, open reading frame 2 protein (ORF2p)¹. ORF2p reverse transcriptase (RT) and endonuclease activities have been implicated in the pathophysiology of cancer^2,3, autoimmunity^4,5 and ageing^6,7, making ORF2p a potential therapeutic target. However, a lack of structural and mechanistic knowledge has hampered efforts to rationally exploit it. We report structures of the human ORF2p 'core' (residues 238-1061, including the RT domain) by X-ray crystallography and cryo-electron microscopy in several conformational states. Our analyses identified two previously undes

SUBMITTER: Baldwin ET 

PROVIDER: S-EPMC10830420 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature