6fia
From Proteopedia
Structure of the human LINE-1 ORF1p coiled coil domain
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 PubMedLINE-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
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