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

Publication date: 18 July 2017
Source:Cell Reports, Volume 20, Issue 3
Author(s): Ivan B. Lomakin, Elena A. Stolboushkina, Anand T. Vaidya, Chenguang Zhao, Maria B. Garber, Sergey E. Dmitriev, Thomas A. Steitz
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.

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Teaser

Some HCV-like viruses and specific cellular mRNAs use the DENR-MCT-1 heterodimer to initiate protein synthesis by an unknown mechanism. Lomakin et al. determined by X-ray crystallography the binding interface between the human small ribosomal subunit and the DENR-MCT-1 heterodimer, which is important for the DENR-MCT-1 function in non-canonical translation initiation and reinitiation.


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