6yan
Mammalian 48S late-stage translation initiation complex with histone 4 mRNA
Structural highlights
FunctionRS3_RABIT Component of the small ribosomal subunit (PubMed:23873042, PubMed:25601755, PubMed:26245381, PubMed:27863242). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23873042, PubMed:25601755, PubMed:26245381, PubMed:27863242). Has endonuclease activity and plays a role in repair of damaged DNA (By similarity). Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA (By similarity). Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS) (By similarity). Has also been shown to bind with similar affinity to intact and damaged DNA (By similarity). Stimulates the N-glycosylase activity of the base excision protein OGG1 (By similarity). Enhances the uracil excision activity of UNG1 (By similarity). Also stimulates the cleavage of the phosphodiester backbone by APEX1 (By similarity). When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage (By similarity). Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide (By similarity). Plays a role in regulating transcription as part of the NF-kappa-B p65-p50 complex where it binds to the RELA/p65 subunit, enhances binding of the complex to DNA and promotes transcription of target genes (By similarity). Represses its own translation by binding to its cognate mRNA (By similarity). Binds to and protects TP53/p53 from MDM2-mediated ubiquitination (By similarity). Involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization (By similarity). Involved in induction of apoptosis through its role in activation of CASP8 (By similarity). Induces neuronal apoptosis by interacting with the E2F1 transcription factor and acting synergistically with it to up-regulate pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (By similarity). Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation (By similarity).[UniProtKB:P23396][1] [2] [3] [4] Publication Abstract from PubMedIn higher eukaryotes, the mRNA sequence in the direct vicinity of the start codon, called the Kozak sequence (CRCCaugG, where R is a purine), is known to influence the rate of the initiation process. However, the molecular basis underlying its role remains poorly understood. Here, we present the cryoelectron microscopy (cryo-EM) structures of mammalian late-stage 48S initiation complexes (LS48S ICs) in the presence of two different native mRNA sequences, beta-globin and histone 4, at overall resolution of 3 and 3.5 A, respectively. Our high-resolution structures unravel key interactions from the mRNA to eukaryotic initiation factors (eIFs): 1A, 2, 3, 18S rRNA, and several 40S ribosomal proteins. In addition, we are able to study the structural role of ABCE1 in the formation of native 48S ICs. Our results reveal a comprehensive map of ribosome/eIF-mRNA and ribosome/eIF-tRNA interactions and suggest the impact of mRNA sequence on the structure of the LS48S IC. Structural Insights into the Mammalian Late-Stage Initiation Complexes.,Simonetti A, Guca E, Bochler A, Kuhn L, Hashem Y Cell Rep. 2020 Apr 7;31(1):107497. doi: 10.1016/j.celrep.2020.03.061. PMID:32268096[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also
References
| ||||||||||||||||||||
