6MS4

Crystal structure of the DENR-MCT-1 complex

Summary for 6MS4

• Entry DOI: 10.2210/pdb6ms4/pdb
• Descriptor: Malignant T-cell-amplified sequence 1, Density-regulated protein, TRIETHYLENE GLYCOL, ... (7 entities in total)
• Functional Keywords: reinitiation, ribosome, zinc binding, trna binding, translation
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 26704.65

Authors

Lomakin, I.B.,Steitz, T.A.,Dmitriev, S.E. (deposition date: 2018-10-16, release date: 2019-01-02, Last modification date: 2024-11-06)

Primary citation

Lomakin, I.B.,Dmitriev, S.E.,Steitz, T.A.
Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation.
Proc. Natl. Acad. Sci. U.S.A., 116:528-533, 2019

PubMed Abstract: 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.

PubMed: 30584092
DOI: 10.1073/pnas.1809688116

Experimental method

X-RAY DIFFRACTION (2.001 Å)