Justin A. Grennell, Kendra D. Jenkins, Kelvin B. Luther, John Glushka, Robert S. Haltiwanger, Megan A. Macnaughtan
{"title":"小鼠NOTCH1 EGF27的1H, 15N, 13C骨干和侧链共振分配和二级结构","authors":"Justin A. Grennell, Kendra D. Jenkins, Kelvin B. Luther, John Glushka, Robert S. Haltiwanger, Megan A. Macnaughtan","doi":"10.1007/s12104-022-10116-0","DOIUrl":null,"url":null,"abstract":"<div><p>NOTCH1 is a transmembrane receptor in metazoans that is linked to a variety of disorders. The receptor contains an extracellular domain (ECD) with 36 tandem epidermal growth factor-like (EGF) repeats. The ECD is responsible for intercellular signaling via protein–ligand interactions with neighboring cells. Each EGF repeat consists of approximately 40 amino acids and 3 conserved disulfide bonds. The <i>Abruptex</i> region (EGF24-29) is critical for NOTCH1 signaling and is known for its missense mutations. Certain EGF repeats are modified with the addition of <i>O</i>-linked glycans and many have calcium binding sites, which give each EGF repeat a unique function. It has been shown that the loss of the <i>O</i>-fucose site of EGF27 alters NOTCH1 activity. To investigate the role of glycosylation in the NOTCH1 signaling pathway, nuclear magnetic resonance spectroscopy has been employed to study the structures of EGF27 and its glycoforms. Here, we report the backbone and sidechain <sup>1</sup>H, <sup>15</sup>N, and <sup>13</sup>C-resonance assignments of the unmodified EGF27 protein and the predicted secondary structure derived from the assigned chemical shifts.\n</p></div>","PeriodicalId":492,"journal":{"name":"Biomolecular NMR Assignments","volume":null,"pages":null},"PeriodicalIF":0.8000,"publicationDate":"2022-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12104-022-10116-0.pdf","citationCount":"0","resultStr":"{\"title\":\"1H, 15N, 13C backbone and sidechain resonance assignments and secondary structure of mouse NOTCH1 EGF27\",\"authors\":\"Justin A. Grennell, Kendra D. Jenkins, Kelvin B. Luther, John Glushka, Robert S. Haltiwanger, Megan A. Macnaughtan\",\"doi\":\"10.1007/s12104-022-10116-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>NOTCH1 is a transmembrane receptor in metazoans that is linked to a variety of disorders. The receptor contains an extracellular domain (ECD) with 36 tandem epidermal growth factor-like (EGF) repeats. The ECD is responsible for intercellular signaling via protein–ligand interactions with neighboring cells. Each EGF repeat consists of approximately 40 amino acids and 3 conserved disulfide bonds. The <i>Abruptex</i> region (EGF24-29) is critical for NOTCH1 signaling and is known for its missense mutations. Certain EGF repeats are modified with the addition of <i>O</i>-linked glycans and many have calcium binding sites, which give each EGF repeat a unique function. It has been shown that the loss of the <i>O</i>-fucose site of EGF27 alters NOTCH1 activity. To investigate the role of glycosylation in the NOTCH1 signaling pathway, nuclear magnetic resonance spectroscopy has been employed to study the structures of EGF27 and its glycoforms. Here, we report the backbone and sidechain <sup>1</sup>H, <sup>15</sup>N, and <sup>13</sup>C-resonance assignments of the unmodified EGF27 protein and the predicted secondary structure derived from the assigned chemical shifts.\\n</p></div>\",\"PeriodicalId\":492,\"journal\":{\"name\":\"Biomolecular NMR Assignments\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.8000,\"publicationDate\":\"2022-12-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://link.springer.com/content/pdf/10.1007/s12104-022-10116-0.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomolecular NMR Assignments\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s12104-022-10116-0\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOPHYSICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomolecular NMR Assignments","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s12104-022-10116-0","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOPHYSICS","Score":null,"Total":0}
1H, 15N, 13C backbone and sidechain resonance assignments and secondary structure of mouse NOTCH1 EGF27
NOTCH1 is a transmembrane receptor in metazoans that is linked to a variety of disorders. The receptor contains an extracellular domain (ECD) with 36 tandem epidermal growth factor-like (EGF) repeats. The ECD is responsible for intercellular signaling via protein–ligand interactions with neighboring cells. Each EGF repeat consists of approximately 40 amino acids and 3 conserved disulfide bonds. The Abruptex region (EGF24-29) is critical for NOTCH1 signaling and is known for its missense mutations. Certain EGF repeats are modified with the addition of O-linked glycans and many have calcium binding sites, which give each EGF repeat a unique function. It has been shown that the loss of the O-fucose site of EGF27 alters NOTCH1 activity. To investigate the role of glycosylation in the NOTCH1 signaling pathway, nuclear magnetic resonance spectroscopy has been employed to study the structures of EGF27 and its glycoforms. Here, we report the backbone and sidechain 1H, 15N, and 13C-resonance assignments of the unmodified EGF27 protein and the predicted secondary structure derived from the assigned chemical shifts.
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.