Crystal structure of the C-terminal domain of DENR

Lomakin, Ivan B.; De, Swastik; Wang, Jimin; Borkar, Aditi N.; Steitz, Thomas A.

Abstract

© 2020 The Authors 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.

Citation

Lomakin, I. B., De, S., Wang, J., Borkar, A. N., & Steitz, T. A. (2020). Crystal structure of the C-terminal domain of DENR. Computational and Structural Biotechnology Journal, 18, 696-704. https://doi.org/10.1016/j.csbj.2020.03.009

• Journal Article Type: Article
• Acceptance Date: Mar 11, 2020
• Online Publication Date: Mar 30, 2020
• Publication Date: 2020
• Deposit Date: Sep 8, 2022
• Publicly Available Date: Sep 8, 2022
• Journal: Computational and Structural Biotechnology Journal
• Electronic ISSN: 2001-0370
• Publisher: Research Network of Computational and Structural Biotechnology
• Peer Reviewed: Peer Reviewed
• Volume: 18
• Pages: 696-704
• DOI: https://doi.org/10.1016/j.csbj.2020.03.009
• Keywords: Computer Science Applications; Genetics; Biochemistry; Structural Biology; Biophysics; Biotechnology
• Public URL: https://nottingham-repository.worktribe.com/output/5274451
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2001037020300477?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: Crystal structure of the C-terminal domain of DENR; Journal Title: Computational and Structural Biotechnology Journal; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.csbj.2020.03.009; Content Type: article; Copyright: © 2020 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.