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

Nucleic Acids Res. 2013 Dec;41(22):10563-72. doi: 10.1093/nar/gkt786. Epub 2013 Sep 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Esterases / chemistry*
  • Esterases / genetics
  • Esterases / metabolism
  • Fatty Acids / chemistry
  • Liposomes
  • Models, Molecular
  • Molecular Sequence Data
  • Phospholipids / metabolism
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Retroelements*
  • Zebrafish / genetics
  • Zebrafish Proteins / chemistry*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Fatty Acids
  • Liposomes
  • ORF1 protein, zebrafish
  • Phospholipids
  • Retroelements
  • Zebrafish Proteins
  • Esterases