7qe0
80S-bound human SKI complex in the open state
Structural highlights
DiseaseSKI2_HUMAN Syndromic diarrhea. The disease is caused by variants affecting the gene represented in this entry. FunctionSKI2_HUMAN Helicase component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways (PubMed:16024656, PubMed:32006463, PubMed:35120588). The SKI complex catalyzes mRNA extraction from 80S ribosomal complexes in the 3'-5' direction and channels mRNA to the cytosolic exosome for degradation (PubMed:32006463, PubMed:35120588). SKI-mediated extraction of mRNA from stalled ribosomes allow binding of the Pelota-HBS1L complex and subsequent ribosome disassembly by ABCE1 for ribosome recycling (PubMed:32006463). In the nucleus, the SKI complex associates with transcriptionally active genes in a manner dependent on PAF1 complex (PAF1C) (PubMed:16024656).[1] [2] [3] Publication Abstract from PubMedThe superkiller (SKI) complex is the cytoplasmic co-factor and regulator of the RNA-degrading exosome. In human cells, the SKI complex functions mainly in co-translational surveillance-decay pathways, and its malfunction is linked to a severe congenital disorder, the trichohepatoenteric syndrome. To obtain insights into the molecular mechanisms regulating the human SKI (hSKI) complex, we structurally characterized several of its functional states in the context of 80S ribosomes and substrate RNA. In a prehydrolytic ATP form, the hSKI complex exhibits a closed conformation with an inherent gating system that effectively traps the 80S-bound RNA into the hSKI2 helicase subunit. When active, hSKI switches to an open conformation in which the gating is released and the RNA 3' end exits the helicase. The emerging picture is that the gatekeeping mechanism and architectural remodeling of hSKI underpin a regulated RNA channeling system that is mechanistically conserved among the cytoplasmic and nuclear helicase-exosome complexes. The human SKI complex regulates channeling of ribosome-bound RNA to the exosome via an intrinsic gatekeeping mechanism.,Kogel A, Keidel A, Bonneau F, Schafer IB, Conti E Mol Cell. 2022 Feb 17;82(4):756-769.e8. doi: 10.1016/j.molcel.2022.01.009. Epub , 2022 Feb 3. PMID:35120588[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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