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The direction of protein entry into the proteasome determines the variety of products and depends on the force needed to unfold its two termini.
Berko, Dikla; Tabachnick-Cherny, Shira; Shental-Bechor, Dalit; Cascio, Paolo; Mioletti, Silvia; Levy, Yaakov; Admon, Arie; Ziv, Tamar; Tirosh, Boaz; Goldberg, Alfred L; Navon, Ami.
Afiliação
  • Berko D; Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
Mol Cell ; 48(4): 601-11, 2012 Nov 30.
Article em En | MEDLINE | ID: mdl-23041283
ABSTRACT
Poorly structured domains in proteins enhance their susceptibility to proteasomal degradation. To learn whether the presence of such a domain near either end of a protein determines its direction of entry into the proteasome, directional translocation was enforced on several proteasome substrates. Using archaeal PAN-20S complexes, mammalian 26S proteasomes, and cultured cells, we identified proteins that are degraded exclusively from either the C or N terminus and some showing no directional preference. This property results from interactions of the substrate's termini with the regulatory ATPase and could be predicted based on the calculated relative stabilities of the N and C termini. Surprisingly, the direction of entry into the proteasome affected markedly the spectrum of peptides released and consequently influenced the efficiency of MHC class I presentation. Thus, easily unfolded termini are translocated first, and the direction of translocation influences the peptides generated and presented to the immune system.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas / Complexo de Endopeptidases do Proteassoma / Desdobramento de Proteína Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas / Complexo de Endopeptidases do Proteassoma / Desdobramento de Proteína Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2012 Tipo de documento: Article