6FIA

Structure of the human LINE-1 ORF1p coiled coil domain

Summary for 6FIA

• Entry DOI: 10.2210/pdb6fia/pdb
• Related: 2w7a 2yko 2ykp 2ykq
• Descriptor: LINE-1 retrotransposable element ORF1 protein, CHLORIDE ION (3 entities in total)
• Functional Keywords: rna binding protein, coiled coil, genome evolution, nucleic acid chaperone, retrotransposition, rnp
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus, nucleolus : Q9UN81
• Total number of polymer chains: 6
• Total formula weight: 75725.23

Authors

Khazina, E.,Weichenrieder, O. (deposition date: 2018-01-17, release date: 2018-03-28, Last modification date: 2024-01-17)

Primary citation

Khazina, E.,Weichenrieder, O.
Human LINE-1 retrotransposition requires a metastable coiled coil and a positively charged N-terminus in L1ORF1p.
Elife, 7:-, 2018

PubMed Abstract: 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.

PubMed: 29565245
DOI: 10.7554/eLife.34960

Experimental method

X-RAY DIFFRACTION (2.65 Å)