8XP2

Cryo-EM structure of the human 40S ribosome with LARP1

This is a non-PDB format compatible entry.

Summary for 8XP2

• Entry DOI: 10.2210/pdb8xp2/pdb
• EMDB information: 38548
• Descriptor: 60S ribosomal protein L41, 40S ribosomal protein S10, 40S ribosomal protein S11, ... (37 entities in total)
• Functional Keywords: 40s ribosome, larp1, mtor, ribosome
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 36
• Total formula weight: 1349401.33

Authors

Huang, Z.,Ye, X.,Li, Y.,Cheng, J. (deposition date: 2024-01-02, release date: 2024-11-20, Last modification date: 2025-01-01)

Primary citation

Saba, J.A.,Huang, Z.,Schole, K.L.,Ye, X.,Bhatt, S.D.,Li, Y.,Timp, W.,Cheng, J.,Green, R.
LARP1 binds ribosomes and TOP mRNAs in repressed complexes.
Embo J., 43:6555-6572, 2024

PubMed Abstract: Terminal oligopyrimidine motif-containing mRNAs (TOPs) encode all ribosomal proteins in mammals and are regulated to tune ribosome synthesis to cell state. Previous studies have implicated LARP1 in 40S- or 80S-ribosome complexes that are thought to repress and stabilize TOPs. However, a molecular understanding of how LARP1 and TOPs interact with these ribosome complexes is lacking. Here, we show that LARP1 directly binds non-translating ribosomal subunits. Cryo-EM structures reveal a previously uncharacterized domain of LARP1 bound to and occluding the mRNA channel of the 40S subunit. Increased availability of free ribosomal subunits downstream of various stresses promote 60S joining at the same interface to form LARP1-80S complexes. Simultaneously, LARP1 engages the TOP via its previously characterized La/PAM2 and DM15 domains. Contrary to expectations, ribosome binding within these complexes is not required for LARP1-mediated TOP repression or stabilization, two canonical LARP1 functions. Together, this work provides molecular insight into how LARP1 directly binds ribosomal subunits and challenges existing models describing the function of repressed LARP1-40S/80S-TOP complexes.

PubMed: 39533057
DOI: 10.1038/s44318-024-00294-z

Experimental method

ELECTRON MICROSCOPY (3.2 Å)