2026/01/16 by Ying Zhang, Lorenz Grundmann, Leonie Vollmar +9 · 2 voices
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #ATP hydrolysis #Binding site #Folding (DSP implementation) #Function (biology) #Heat shock proteins research #Plasma protein binding #RNA and protein synthesis mechanisms #Ribosomal protein #Ribosome #Saccharomyces cerevisiae #Toxin Mechanisms and Immunotoxins #Translation (biology) #Yeast
paper · doi:10.1038/s41467-025-67685-6
published in Nature Communications 17(1), 961 (Nature Portfolio)
openalex publication_date 2026/01/16 · openalex created_date 2026/01/17 · openalex updated_date 2026/08/05
Coupling of ribosomal translation with cotranslational protein folding is essential for cellular homeostasis. In eukaryotes, Hsp70 and its J-domain cochaperone, the heterodimeric ribosome-associated complex (RAC), are central to this process; however, mechanistic insights into the coordination of Hsp70 function with translation remain limited. Here, we present two cryo-EM structures of the ribosome-bound yeast Hsp70 Ssb, identifying Rpl25/uL23 as the ribosomal binding site and revealing its interaction with a model nascent chain. Together with detailed biochemical and mutational analyses, these structures enable us to delineate the intricate RAC-dependent cycle, which positions the substrate binding domain of Ssb-ATP close to the tunnel exit to receive nascent chains. This arrangement allows Ssb to undergo substantial conformational changes upon ATP hydrolysis without steric clashes with the ribosome, while the substrate binding domain of Ssb, now anchored by the tightly bound nascent chain, remains close to the tunnel exit.