Structural inventory of cotranslational protein folding by the eukaryotic RAC complex.

Miglė Kišonaitė, Klemens Wild, Karine Lapouge, Genís Valentín Gesé, Nikola Kellner, Ed Hurt, Irmgard Sinning

Nature structural & molecular biology 2023 May

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The challenge of nascent chain folding at the ribosome is met by the conserved ribosome-associated complex (RAC), which forms a chaperone triad with the Hsp70 protein Ssb in fungi, and consists of the non-canonical Hsp70 Ssz1 and the J domain protein Zuotin (Zuo1). Here we determine cryo-EM structures of Chaetomium thermophilum RAC bound to 80S ribosomes. RAC adopts two distinct conformations accommodating continuous ribosomal rotation by a flexible lever arm. It is held together by a tight interaction between the Ssz1 substrate-binding domain and the Zuo1 N terminus, and additional contacts between the Ssz1 nucleotide-binding domain and Zuo1 J- and Zuo1 homology domains, which form a rigid unit. The Zuo1 HPD motif conserved in J-proteins is masked in a non-canonical interaction by the Ssz1 nucleotide-binding domain, and allows the positioning of Ssb for activation by Zuo1. Overall, we provide the basis for understanding how RAC cooperates with Ssb in a dynamic nascent chain interaction and protein folding. © 2023. The Author(s).

Citation

Miglė Kišonaitė, Klemens Wild, Karine Lapouge, Genís Valentín Gesé, Nikola Kellner, Ed Hurt, Irmgard Sinning. Structural inventory of cotranslational protein folding by the eukaryotic RAC complex. Nature structural & molecular biology. 2023 May;30(5):670-677