Structural highlights
Function
[LORF1_HUMAN] Nucleic acid-binding protein which is essential for retrotransposition of LINE-1 elements in the genome. May function as a nucleic acid chaperone binding its own transcript and therefore preferentially mobilizing the transcript from which they are encoded.[1] [2] [3]
Publication Abstract from PubMed
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.
Human LINE-1 retrotransposition requires a metastable coiled coil and a positively charged N-terminus in L1ORF1p.,Khazina E, Weichenrieder O Elife. 2018 Mar 22;7. pii: 34960. doi: 10.7554/eLife.34960. PMID:29565245[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wei W, Gilbert N, Ooi SL, Lawler JF, Ostertag EM, Kazazian HH, Boeke JD, Moran JV. Human L1 retrotransposition: cis preference versus trans complementation. Mol Cell Biol. 2001 Feb;21(4):1429-39. PMID:11158327 doi:http://dx.doi.org/10.1128/MCB.21.4.1429-1439.2001
- ↑ Callahan KE, Hickman AB, Jones CE, Ghirlando R, Furano AV. Polymerization and nucleic acid-binding properties of human L1 ORF1 protein. Nucleic Acids Res. 2012 Jan;40(2):813-27. doi: 10.1093/nar/gkr728. Epub 2011 Sep , 21. PMID:21937507 doi:http://dx.doi.org/10.1093/nar/gkr728
- ↑ Moran JV, Holmes SE, Naas TP, DeBerardinis RJ, Boeke JD, Kazazian HH Jr. High frequency retrotransposition in cultured mammalian cells. Cell. 1996 Nov 29;87(5):917-27. PMID:8945518
- ↑ Khazina E, Weichenrieder O. Human LINE-1 retrotransposition requires a metastable coiled coil and a positively charged N-terminus in L1ORF1p. Elife. 2018 Mar 22;7. pii: 34960. doi: 10.7554/eLife.34960. PMID:29565245 doi:http://dx.doi.org/10.7554/eLife.34960
