Download MendeleyThe La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence.
Lahr, R.M., Mack, S.M., Heroux, A., Blagden, S.P., Bousquet-Antonelli, C., Deragon, J.M., Berman, A.J.(2015) Nucleic Acids Res 43: 8077-8088
- PubMed: 26206669
- DOI: https://doi.org/10.1093/nar/gkv748
- Primary Citation of Related Structures:
4ZC4, 5C0V - PubMed Abstract:
La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include 5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode ribosomal proteins and translation factors. We determined that the highly conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a 5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 Å resolution has three structurally related and evolutionarily conserved helix-turn-helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous helical protein-binding structures, but their sequences are inconsistent with consensus sequences of known HEAT modules, suggesting this structure has been repurposed for RNA interactions. A putative mTORC1-recognition sequence sits within a flexible loop C-terminal to these repeats. We also present modelling of pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15 region. These studies lay the foundation necessary for proceeding toward a structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.
Organizational Affiliation:
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
