6vpr
From Proteopedia
Crystal structure of the C-terminal domain of DENR
Structural highlights
Function[DENR_HUMAN] May be involved in the translation of target mRNAs by scanning and recognition of the initiation codon. Involved in translation initiation; promotes recruitmnet of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits. Plays a role in the modulation of the translational profile of a subset of cancer-related mRNAs when recruited to the translational initiation complex by the oncogene MCTS1.[1] [2] [3] Publication Abstract from PubMedThe 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 A 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. Crystal structure of the C-terminal domain of DENR.,Lomakin IB, De S, Wang J, Borkar AN, Steitz TA Comput Struct Biotechnol J. 2020 Mar 19;18:696-704. doi:, 10.1016/j.csbj.2020.03.009. eCollection 2020. PMID:32257053[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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