7qws
From Proteopedia
Structure of ribosome translating beta-tubulin in complex with TTC5 and NAC
Structural highlights
FunctionNACA_HUMAN Prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. Also reduces the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites). May act as a specific coactivator for JUN, binding to DNA and stabilizing the interaction of JUN homodimers with target gene promoters.[1] [2] [3] Publication Abstract from PubMedThe nascent polypeptide-associated complex (NAC) interacts with newly synthesized proteins at the ribosomal tunnel exit and competes with the signal recognition particle (SRP) to prevent mistargeting of cytosolic and mitochondrial polypeptides to the endoplasmic reticulum (ER). How NAC antagonizes SRP and how this is overcome by ER targeting signals are unknown. Here, we found that NAC uses two domains with opposing effects to control SRP access. The core globular domain prevented SRP from binding to signal-less ribosomes, whereas a flexibly attached domain transiently captured SRP to permit scanning of nascent chains. The emergence of an ER-targeting signal destabilized NAC's globular domain and facilitated SRP access to the nascent chain. These findings elucidate how NAC hands over the signal sequence to SRP and imparts specificity of protein localization. Mechanism of signal sequence handover from NAC to SRP on ribosomes during ER-protein targeting.,Jomaa A, Gamerdinger M, Hsieh HH, Wallisch A, Chandrasekaran V, Ulusoy Z, Scaiola A, Hegde RS, Shan SO, Ban N, Deuerling E Science. 2022 Feb 25;375(6583):839-844. doi: 10.1126/science.abl6459. Epub 2022 , Feb 24. PMID:35201867[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Oryctolagus cuniculus | Ban N | Chandrasekaran V | Deuerling E | Gamerdinger M | Hegde R | Hsieh H | Jomaa A | Scaiola A | Shan S | Ulusoy Z | Wallisch A
