Cryo-EM structure of the AAA+ SPATA5 complex and its role in human cytoplasmic pre-60S maturation
Year: 2025
Type: article
Abstract: Eukaryotic ribosome biogenesis is an energy-consuming process involving many ATPase-driven steps. In yeast, AAA+ protein Drg1 releases an assembly factor Rlp24, a placeholder for Rpl24, from pre-60S particles just exported to cytosol. The equivalent process in human cells involves SPATA5 (Drg1 homolog) and additional factors. However, the mechanistic details remain unclear. Here we reveal that SPATA5 forms a 4:2:2:2 complex with SPATA5L1, C1orf109, and CINP. This complex features an N-terminal ring made of C1orf109, CINP and NTDs of SPATA5/SPATA5L1, and two hexameric AAA+ ATPase rings. Intriguingly, a conserved cysteine C672 in the P-loop of SPATA5 is sulfinylated, generating an inactive conformation incompatible with ATP binding. We also obtained a cryo-EM structure of pre-60S-bound SPATA5 complex. Different from yeast, the recognition of the pre-60S particle is mediated by human-specific factor CINP, through two distinct sets of interactions: one with GTPBP4 and the other with ES27A. Taken together, these data provide structural basis for understanding the cytoplasmic maturation of the pre-60S, and reveal human-specific features that might be harnessed for therapeutic purposes. Eukaryotic ribosome assembly involves multiple AAA+ ATPase hexamer mediated maturation steps. Here, authors report the structural analysis of the human SPATA5/SPATA5L1/CINP/C1ORF109 ATPase complex, revealing its role in cytoplasmic pre-60S maturation.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Award: G2776607833
OpenAlex ID: W4409696294