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Investigating the Line-1 ORF2 C-Terminal Domain

Description

Abstract:
Long Interspersed Nuclear Element-1 (LINE-1 or L1) is the only active autonomously replicating retrotransposon in humans, comprising approximately 17% of the genome [1]. While normally transcriptionally repressed, L1 expression increases with age and contributes to genomic instability, sterile inflammation, and other age-associated phenotypes. The L1 element encodes two proteins, the RNA-binding chaperone ORF1 and the ORF2 protein, which contains endonuclease, reverse transcriptase, and C-terminal cysteine-rich domain (CTD) that contains a predicted zinc knuckle structure. While the CTD has unknown structure and function, mutations to the CTD cause a disruption in LINE-1 retrotransposition. It has been hypothesized that the CTD plays a role in the binding of ORF2 to RNA to create ribonucleic particles that are probable intermediates of retrotransposition [2,3]. However, without knowing the structure or domain boundaries of the CTD, it is difficult to explain its interaction with RNA and to create stable protein constructs to study this interaction in vitro. Here, I use in-silico methods such as homology modeling, de novo modeling, and molecular dynamics simulations to propose and validate a probable model for L1 ORF2 CTD.

Citation

Ashley E Battenberg, "Investigating the Line-1 ORF2 C-Terminal Domain" (2020). Summer Research Symposium. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/667r-r420

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Collection:

  • Summer Research Symposium

    Each year, Brown University showcases the research of its undergraduates at the Summer Research Symposium. More than half of the student-researchers are UTRA recipients, while others receive funding from a variety of Brown-administered and national programs and fellowships and go …
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