title: Structure and properties of the esterase from non-LTR retrotransposons suggest a role for lipids in retrotransposition.
abstract: Non-LTR retrotransposons are mobile genetic elements and play a major role in eukaryotic genome evolution and disease. Similar to retroviruses they encode a reverse transcriptase, but their genomic integration mechanism is fundamentally different, and they lack homologs of the retroviral nucleocapsid-forming protein Gag. Instead, their first open reading frames encode distinct multi-domain proteins (ORF1ps) presumed to package the retrotransposon-encoded RNA into ribonucleoprotein particles (RNPs). The mechanistic roles of ORF1ps are poorly understood, particularly of ORF1ps that appear to harbor an enzymatic function in the form of an SGNH-type lipolytic acetylesterase. We determined the crystal structures of the coiled coil and esterase domains of the ORF1p from the Danio rerio ZfL2-1 element. We demonstrate a dimerization of the coiled coil and a hydrolytic activity of the esterase. Furthermore, the esterase binds negatively charged phospholipids and liposomes, but not oligo-(A) RNA. Unexpectedly, the esterase can split into two dynamic half-domains, suited to engulf long fatty acid substrates extending from the active site. These properties indicate a role for lipids and membranes in non-LTR retrotransposition. We speculate that Gag-like membrane targeting properties of ORF1ps could play a role in RNP assembly and in membrane-dependent transport or localization processes.
authors.affiliation: Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen, Germany and Friedrich Miescher Laboratory of the Max Planck Society, Spemannstrasse 39, 72076 Tübingen, Germany.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Schneider
authors.forename: Steffen
authors.initials: S
authors.lastname: Schmidt
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jonas
authors.forename: Benjamin
authors.initials: B
authors.lastname: Vollmer
authors.forename: Elena
authors.initials: E
authors.lastname: Khazina
authors.forename: Oliver
authors.initials: O
authors.lastname: Weichenrieder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004950:Esterases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry; D008081:Liposomes; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000378:metabolism; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D018626:Retroelements; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D008081:Liposomes; C572669:ORF1 protein, zebrafish; D010743:Phospholipids; D018626:Retroelements; D029961:Zebrafish Proteins; D004950:Esterases