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TitleStructural inventory of cotranslational protein folding by the eukaryotic RAC complex.
Journal, issue, pagesNat Struct Mol Biol, Vol. 30, Issue 5, Page 670-677, Year 2023
Publish dateApr 20, 2023
AuthorsMiglė Kišonaitė / Klemens Wild / Karine Lapouge / Genís Valentín Gesé / Nikola Kellner / Ed Hurt / Irmgard Sinning /
PubMed AbstractThe 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 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.
External linksNat Struct Mol Biol / PubMed:37081320 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.3 Å
Structure data

14479

7z3n

EMDB-14479, PDB-7z3n:
Cryo-EM structure of the ribosome-associated RAC complex on the 80S ribosome - RAC-1 conformation
Method: EM (single particle) / Resolution: 3.2 Å

14480

7z3o

EMDB-14480, PDB-7z3o:
Cryo-EM structure of the ribosome-associated RAC complex on the 80S ribosome - RAC-2 conformation
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-ZN:
Unknown entry

Source
  • Chaetomium thermophilum var. thermophilum DSM 1495 (fungus)
  • thermochaetoides thermophila dsm 1495 (fungus)
KeywordsCHAPERONE / RAC / ribosome-associated complex / thermophilic eukaryotic ribosome / 80S

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