Structure and properties of the esterase from non-LTR retrotransposons suggest a role for lipids in retrotransposition

摘要: Non-LTR retrotransposons are mobile genetic elements and play a major role in eukaryotic genome evolution disease. Similar to retroviruses they encode reverse transcriptase, but their genomic integration mechanism is fundamentally different, lack homologs of the retroviral nucleocapsid-forming protein Gag. Instead, first open reading frames distinct multi-domain proteins (ORF1ps) presumed package retrotransposon-encoded RNA into ribonucleoprotein particles (RNPs). The mechanistic roles ORF1ps poorly understood, particularly that appear harbor an enzymatic function form SGNH-type lipolytic acetylesterase. We determined crystal structures coiled coil esterase domains ORF1p from Danio rerio ZfL2-1 element. demonstrate dimerization hydrolytic activity esterase. Furthermore, binds negatively charged phospholipids liposomes, not oligo-(A) RNA. Unexpectedly, can split two dynamic half-domains, suited engulf long fatty acid substrates extending active site. These properties indicate for lipids membranes non-LTR retrotransposition. speculate Gag-like membrane targeting could RNP assembly membrane-dependent transport or localization processes.