Human LINE-1 retrotransposition requires a metastable coiled coil and a positively charged N-terminus in L1ORF1p

Elife. 2018 Mar 22:7:e34960. doi: 10.7554/eLife.34960.


LINE-1 (L1) is an autonomous retrotransposon, which acted throughout mammalian evolution and keeps contributing to human genotypic diversity, genetic disease and cancer. L1 encodes two essential proteins: L1ORF1p, a unique RNA-binding protein, and L1ORF2p, an endonuclease and reverse transcriptase. L1ORF1p contains an essential, but rapidly evolving N-terminal portion, homo-trimerizes via a coiled coil and packages L1RNA into large assemblies. Here, we determined crystal structures of the entire coiled coil domain of human L1ORF1p. We show that retrotransposition requires a non-ideal and metastable coiled coil structure, and a strongly basic L1ORF1p amino terminus. Human L1ORF1p therefore emerges as a highly calibrated molecular machine, sensitive to mutation but functional in different hosts. Our analysis rationalizes the locally rapid L1ORF1p sequence evolution and reveals striking mechanistic parallels to coiled coil-containing membrane fusion proteins. It also suggests how trimeric L1ORF1p could form larger meshworks and indicates critical novel steps in L1 retrotransposition.

Keywords: LINE; chromosomes; coiled coil; conformational dynamics; gene expression; human; mobile DNA; molecular biophysics; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Humans
  • Long Interspersed Nucleotide Elements / genetics*
  • Models, Molecular
  • Mutagenesis, Insertional
  • Mutation
  • Protein Conformation
  • Protein Multimerization*
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribonucleoproteins / chemistry*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism
  • Sequence Homology, Amino Acid


  • L1 ORF1 protein, human
  • RNA-Binding Proteins
  • Ribonucleoproteins

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.