Conformational flexibility within the nascent polypeptide-associated complex enables its interactions with structurally diverse client proteins.
J Biol Chem
; 293(22): 8554-8568, 2018 06 01.
Article
en En
| MEDLINE
| ID: mdl-29650757
As newly synthesized polypeptides emerge from the ribosome, it is crucial that they fold correctly. To prevent premature aggregation, nascent chains interact with chaperones that facilitate folding or prevent misfolding until protein synthesis is complete. Nascent polypeptide-associated complex (NAC) is a ribosome-associated chaperone that is important for protein homeostasis. However, how NAC binds its substrates remains unclear. Using native electrospray ionization MS (ESI-MS), limited proteolysis, NMR, and cross-linking, we analyzed the conformational properties of NAC from Caenorhabditis elegans and studied its ability to bind proteins in different conformational states. Our results revealed that NAC adopts an array of compact and expanded conformations and binds weakly to client proteins that are unfolded, folded, or intrinsically disordered, suggestive of broad substrate compatibility. Of note, we found that this weak binding retards aggregation of the intrinsically disordered protein α-synuclein both in vitro and in vivo These findings provide critical insights into the structure and function of NAC. Specifically, they reveal the ability of NAC to exploit its conformational plasticity to bind a repertoire of substrates with unrelated sequences and structures, independently of actively translating ribosomes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
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Biosíntesis de Proteínas
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Caenorhabditis elegans
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Chaperonas Moleculares
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Proteínas de Caenorhabditis elegans
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Sinucleínas
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2018
Tipo del documento:
Article
Pais de publicación:
Estados Unidos