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Cell Rep. 2017 Jul 18;20(3):521-528. doi: 10.1016/j.celrep.2017.06.025.

Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1.

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA. Electronic address: ivan.lomakin@yale.edu.
2
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
3
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA.
4
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
5
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia.
6
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520-8114, USA. Electronic address: thomas.steitz@yale.edu.

Abstract

The repertoire of the density-regulated protein (DENR) and the malignant T cell-amplified sequence 1 (MCT-1/MCTS1) oncoprotein was recently expanded to include translational control of a specific set of cancer-related mRNAs. DENR and MCT-1 form the heterodimer, which binds to the ribosome and operates at both translation initiation and reinitiation steps, though by a mechanism that is yet unclear. Here, we determined the crystal structure of the human small ribosomal subunit in complex with DENR-MCT-1. The structure reveals the location of the DENR-MCT-1 dimer bound to the small ribosomal subunit. The binding site of the C-terminal domain of DENR on the ribosome has a striking similarity with those of canonical initiation factor 1 (eIF1), which controls the fidelity of translation initiation and scanning. Our findings elucidate how the DENR-MCT-1 dimer interacts with the ribosome and have functional implications for the mechanism of unconventional translation initiation and reinitiation.

KEYWORDS:

density regulated protein; malignant T cell-amplified sequence 1; protein synthesis; ribosome; translation initiation; translation reinitiation

PMID:
28723557
PMCID:
PMC5551485
DOI:
10.1016/j.celrep.2017.06.025
[Indexed for MEDLINE]
Free PMC Article

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