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

Cell Reports

Thomas A. Steitz¹  Ivan B. Lomakin¹  Anand T. Vaidya¹  Chenguang Zhao¹  Sergey E. Dmitriev²  Elena A. Stolboushkina³  Maria B. Garber³ 

[1] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8114, USA;Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia;Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia;

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

DOI  :  10.1016/j.celrep.2017.06.025

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown