mRNA结合蛋白hnRNP A18的1H, 13C和15N分配

IF 0.8 4区 生物学 Q4 BIOPHYSICS
Katherine M. Coburn, Braden Roth, Kristen M. Varney, France Carrier, David J. Weber
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引用次数: 1

摘要

异质核糖核蛋白A18 (hnRNP A18)是一种RNA结合蛋白(RBP),在黑色素瘤、乳腺癌、前列腺癌和结肠癌实体瘤中参与缺氧细胞应激反应和细胞毒性t淋巴细胞相关蛋白4 (CTLA-4)表达的调节。hnRNP A18由一个n端结构化RNA识别基序(RMM)和一个c端内在无序结构域(IDD)组成。在低温胁迫条件下,如紫外线和缺氧,hnRNP A18被酪蛋白激酶2 (CK2)和糖原合成酶激酶3β (GSK-3β)磷酸化。磷酸化后,hnRNP A18从细胞核转运到细胞质,在那里它与促存活mRNA转录物相互作用,如缺氧诱导因子1α和CTLA-4。低氧细胞反应和癌细胞免疫检查点的调节都促进了放化疗抵抗和转移。在这项研究中,172个氨基酸hnRNP A18的1 H、13 C和15 N的主链和侧链共振被指定为序列特异性,并为未来针对hnRNP A18的基于nmr的药物发现研究提供了框架。这些数据也将使研究hnRNP A18被CK2和GSK-3β磷酸化后IDD内的动态结构变化成为可能,从而为IDD的结构和功能提供关键的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

1H, 13C, and 15N assignments of the mRNA binding protein hnRNP A18

1H, 13C, and 15N assignments of the mRNA binding protein hnRNP A18

Heterogeneous ribonuclear protein A18 (hnRNP A18) is an RNA binding protein (RBP) involved in the hypoxic cellular stress response and regulation of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in melanoma, breast cancer, prostate cancer, and colon cancer solid tumors. hnRNP A18 is comprised of an N-terminal structured RNA recognition motif (RMM) and a C-terminal intrinsically disordered domain (IDD). Upon cellar stressors, such as UV and hypoxia, hnRNP A18 is phosphorylated by casein kinase 2 (CK2) and glycogen synthase kinase 3β (GSK-3β). After phosphorylation, hnRNP A18 translocates from the nucleus to the cytosol where it interacts with pro-survival mRNA transcripts for proteins such as hypoxia inducible factor 1α and CTLA-4. Both the hypoxic cellular response and modulation of immune checkpoints by cancer cells promote chemoradiation resistance and metastasis. In this study, the 1 H, 13 C, and 15 N backbone and sidechain resonances of the 172 amino acid hnRNP A18 were assigned sequence-specifically and provide a framework for future NMR-based drug discovery studies toward targeting hnRNP A18. These data will also enable the investigation of the dynamic structural changes within the IDD of hnRNP A18 upon phosphorylation by CK2 and GSK-3β to provide critical insight into the structure and function of IDDs.

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来源期刊
Biomolecular NMR Assignments
Biomolecular NMR Assignments 生物-光谱学
CiteScore
1.70
自引率
11.10%
发文量
59
审稿时长
6-12 weeks
期刊介绍: Biomolecular NMR Assignments provides a forum for publishing sequence-specific resonance assignments for proteins and nucleic acids as Assignment Notes. Chemical shifts for NMR-active nuclei in macromolecules contain detailed information on molecular conformation and properties. Publication of resonance assignments in Biomolecular NMR Assignments ensures that these data are deposited into a public database at BioMagResBank (BMRB; http://www.bmrb.wisc.edu/), where they are available to other researchers. Coverage includes proteins and nucleic acids; Assignment Notes are processed for rapid online publication and are published in biannual online editions in June and December.
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