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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / chemistry*
  • Crystallography, X-Ray
  • Eukaryotic Initiation Factors / chemistry*
  • Humans
  • Oncogene Proteins / chemistry*
  • Protein Structure, Quaternary
  • Ribosomes / chemistry*


  • Cell Cycle Proteins
  • DENR protein, human
  • Eukaryotic Initiation Factors
  • MCTS1 protein, human
  • Oncogene Proteins