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Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation.
Lomakin, Ivan B; Dmitriev, Sergey E; Steitz, Thomas A.
Afiliação
  • Lomakin IB; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114; ivan.lomakin@yale.edu.
  • Dmitriev SE; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.
  • Steitz TA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114.
Proc Natl Acad Sci U S A ; 116(2): 528-533, 2019 01 08.
Article em En | MEDLINE | ID: mdl-30584092
The density-regulated protein (DENR) and the malignant T cell-amplified sequence 1 (MCT-1/MCTS1) oncoprotein support noncanonical translation initiation, promote translation reinitiation on a specific set of mRNAs with short upstream reading frames, and regulate ribosome recycling. DENR and MCT-1 form a heterodimer, which binds to the ribosome. We determined the crystal structure of the heterodimer formed by human MCT-1 and the N-terminal domain of DENR at 2.0-Å resolution. The structure of the heterodimer reveals atomic details of the mechanism of DENR and MCT-1 interaction. Four conserved cysteine residues of DENR (C34, C37, C44, C53) form a classical tetrahedral zinc ion-binding site, which preserves the structure of the DENR's MCT-1-binding interface that is essential for the dimerization. Substitution of all four cysteines by alanine abolished a heterodimer formation. Our findings elucidate further the mechanism of regulation of DENR-MCT-1 activities in unconventional translation initiation, reinitiation, and recycling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Oncogênicas / Proteínas de Ciclo Celular / Fatores de Iniciação em Eucariotos / Multimerização Proteica Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Oncogênicas / Proteínas de Ciclo Celular / Fatores de Iniciação em Eucariotos / Multimerização Proteica Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article