6VPR

Crystal structure of the C-terminal domain of DENR

Summary for 6VPR

• Entry DOI: 10.2210/pdb6vpr/pdb
• Related: 6VPQ
• Descriptor: Density-regulated protein, L(+)-TARTARIC ACID, SULFATE ION, ... (7 entities in total)
• Functional Keywords: protein synthesis regulation; translation initiation; translation reinitiation; translation recycling; density regulated protein (denr), translation
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 46211.09

Authors

Lomakin, I.B.,Steitz, T.A. (deposition date: 2020-02-04, release date: 2020-04-08, Last modification date: 2024-12-25)

Primary citation

Lomakin, I.B.,De, S.,Wang, J.,Borkar, A.N.,Steitz, T.A.
Crystal structure of the C-terminal domain of DENR.
Comput Struct Biotechnol J, 18:696-704, 2020

PubMed Abstract: The density regulated protein (DENR) forms a stable heterodimer with malignant T-cell-amplified sequence 1 (MCT-1). DENR-MCT-1 heterodimer then participates in regulation of non-canonical translation initiation and ribosomal recycling. The N-terminal domain of DENR interacts with MCT-1 and carries a classical tetrahedral zinc ion-binding site, which is crucial for the dimerization. DENR-MCT-1 binds the small (40S) ribosomal subunit through interactions between MCT-1 and helix h24 of the 18S rRNA, and through interactions between the C-terminal domain of DENR and helix h44 of the 18S rRNA. This later interaction occurs in the vicinity of the P site that is also the binding site for canonical translation initiation factor eIF1, which plays the key role in initiation codon selection and scanning. Sequence homology modeling and a low-resolution crystal structure of the DENR-MCT-1 complex with the human 40S subunit suggests that the C-terminal domain of DENR and eIF1 adopt a similar fold. Here we present the crystal structure of the C-terminal domain of DENR determined at 1.74 Å resolution, which confirms its resemblance to eIF1 and advances our understanding of the mechanism by which DENR-MCT-1 regulates non-canonical translation initiation and ribosomal recycling.

PubMed: 32257053
DOI: 10.1016/j.csbj.2020.03.009

Experimental method

X-RAY DIFFRACTION (2.2 Å)