Sandbox Reserved 931
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*Vertical, wide groove between monomers, with somewhat lower positive local electrostatics. | *Vertical, wide groove between monomers, with somewhat lower positive local electrostatics. | ||
| - | It has been demonstrated by mutagenesis that arginine residues 220, 235 and 261 that are on the surface between the RRM and CTD domains are indispensable for the RNA affinity of the trimer. Therefore, in the RNA-bound state, the RNA is likely wound around the L1ORF1p trunk with the strand passing through the negatively charged vertical and horizontal grooves. So far, however, it is impossible to experimentally verify the structure of the RNA-protein interactions. | + | It has been demonstrated by mutagenesis that arginine residues 220, 235 and 261<ref>[http://nar.oxfordjournals.org/content/39/13/5611.full Evans, Peddigari, Chaurasiya, Williams and Martin]</ref> that are on the surface between the RRM and CTD domains are indispensable for the RNA affinity of the trimer. Therefore, in the RNA-bound state, the RNA is likely wound around the L1ORF1p trunk with the strand passing through the negatively charged vertical and horizontal grooves. So far, however, it is impossible to experimentally verify the structure of the RNA-protein interactions. |
===Structural Flexibility=== | ===Structural Flexibility=== | ||
Revision as of 08:55, 16 May 2014
| This Sandbox is Reserved from 01/04/2014, through 30/06/2014 for use in the course "510042. Protein structure, function and folding" taught by Prof Adrian Goldman, Tommi Kajander, Taru Meri, Konstantin Kogan and Juho Kellosalo at the University of Helsinki. This reservation includes Sandbox Reserved 923 through Sandbox Reserved 947. |
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LINE-1 ORF1 Protein
Long interspersed nuclear element 1 (LINE1) is a non-long terminal repeat (non-LTR) type retrotransposon in mammals that engages in retrotransposition - a process which randomly inserts LINE1's own coding sequence into the host genome, increasing the genome size and causing genomic instability. The LINE1 gene encodes the open reading frame 1 protein (L1ORF1p), which localizes to large L1 ribonucleoprotein particles, stress granules and nucleus (ref), and is required and necessary for retrotransposition.
Introduction
After transcription of the LINE1 gene, the same RNA transcript is both translated and is the template for reverse transcription. This RNA transcript contains two open reading frames: ORF1 and ORF2, which codes for two proteins, ORF1p and ORF2p. L1ORF1p contains the RNA packing and delivery functions, and L1ORF2p contains the enzymatic machinery for reverse transcription. Translation of both of these open reading frames is necessary for retrotransposition. The reverse transcribed LINE1 is integrated into the host genome in a different place than the original gene.
L1ORF1p localizes to ribonucleoprotein particles, stress granules and nucleus. Although the protein has general affinity to nucleic acids, it displays a strong cis preference, which makes it bind the primary encoding RNA transcript[1]. The role of L1ORF1p in retrotransposition is to protect the transcript from degradation and to help transport it to the nucleus.
Structure
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