Cryo-EM structure of the AAA+ SPATA5 complex and its role in human cytoplasmic pre-60S maturation

Yuhao Dai, Damu Wu, Ningning Li, Chengying Ma, Yunyang Zhang () and Ning Gao ()
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Yuhao Dai: Peking University
Damu Wu: Peking University
Ningning Li: Peking University
Chengying Ma: Peking University
Yunyang Zhang: Peking University
Ning Gao: Peking University

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58894-0

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