5V7C

Crystal structure of LARP1-unique domain DM15 bound 5'TOP RNA sequence

Summary for 5V7C

• Entry DOI: 10.2210/pdb5v7c/pdb
• Related: 4ZC4 5V4R 5v87
• Descriptor: La-related protein 1, RNA (5'-R(*CP*UP*UP*UP*UP*CP*CP*G)-3') (3 entities in total)
• Functional Keywords: cap-binding, rna-binding, dm15, 5'top, rna binding protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : Q6PKG0
• Total number of polymer chains: 2
• Total formula weight: 22056.74

Authors

Berman, A.J.,Lahr, R.M.,Al-Ashtal, H.A. (deposition date: 2017-03-20, release date: 2017-04-19, Last modification date: 2023-10-04)

Primary citation

Lahr, R.M.,Fonseca, B.D.,Ciotti, G.E.,Al-Ashtal, H.A.,Jia, J.J.,Niklaus, M.R.,Blagden, S.P.,Alain, T.,Berman, A.J.
La-related protein 1 (LARP1) binds the mRNA cap, blocking eIF4F assembly on TOP mRNAs.
Elife, 6:-, 2017

PubMed Abstract: The 5'terminal oligopyrimidine (5'TOP) motif is a -regulatory RNA element located immediately downstream of the 7-methylguanosine [mG] cap of TOP mRNAs, which encode ribosomal proteins and translation factors. In eukaryotes, this motif coordinates the synchronous and stoichiometric expression of the protein components of the translation machinery. La-related protein 1 (LARP1) binds TOP mRNAs, regulating their stability and translation. We present crystal structures of the human LARP1 DM15 region in complex with a 5'TOP motif, a cap analog (mGTP), and a capped cytidine (mGpppC), resolved to 2.6, 1.8 and 1.7 Å, respectively. Our binding, competition, and immunoprecipitation data corroborate and elaborate on the mechanism of 5'TOP motif binding by LARP1. We show that LARP1 directly binds the cap and adjacent 5'TOP motif of TOP mRNAs, effectively impeding access of eIF4E to the cap and preventing eIF4F assembly. Thus, LARP1 is a specialized TOP mRNA cap-binding protein that controls ribosome biogenesis.

PubMed: 28379136
DOI: 10.7554/eLife.24146

Experimental method

X-RAY DIFFRACTION (2.59 Å)