5C0V

Structure of the LARP1-unique domain DM15

Summary for 5C0V

• Entry DOI: 10.2210/pdb5c0v/pdb
• Related: 4ZC4
• Descriptor: La-related protein 1, SULFATE ION (3 entities in total)
• Functional Keywords: rna-binding, heat-like, mrna, helical repeat, rna binding protein
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q6PKG0
• Total number of polymer chains: 4
• Total formula weight: 79219.99

Authors

Lahr, R.M.,Berman, A.J. (deposition date: 2015-06-12, release date: 2015-08-05, Last modification date: 2024-10-23)

Primary citation

Lahr, R.M.,Mack, S.M.,Heroux, A.,Blagden, S.P.,Bousquet-Antonelli, C.,Deragon, J.M.,Berman, A.J.
The La-related protein 1-specific domain repurposes HEAT-like repeats to directly bind a 5'TOP sequence.
Nucleic Acids Res., 43:8077-8088, 2015

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.

PubMed: 26206669
DOI: 10.1093/nar/gkv748

Experimental method

X-RAY DIFFRACTION (2.2 Å)