来自动点核蛋白 KKT4 的 BRCT 结构域的核磁共振研究。

IF 0.8 4区 生物学 Q4 BIOPHYSICS Biomolecular NMR Assignments Pub Date : 2024-03-07 DOI:10.1007/s12104-024-10163-9
Patryk Ludzia, Hanako Hayashi, Timothy Robinson, Bungo Akiyoshi, Christina Redfield
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引用次数: 0

摘要

KKT4 是一种多域动核蛋白,专属于动核细胞,如布氏锥虫。它与其他真核生物的已知动核蛋白缺乏明显的序列相似性。我们最近对 KKT4 C 端区域的 X 射线结构显示,它有一个串联的 BRCT(BRCA1 C Terminus)结构域折叠,硫酸根离子与磷酸化丝氨酸或苏氨酸的典型结合位点结合。在这里,我们介绍了布鲁氏菌 KKT4(KKT4463-645)BRCT 结构域的 1H、13C 和 15N 共振分配。我们利用 X 射线结构中参与硫酸根离子结合的残基,证明 BRCT 结构域能在溶液中结合磷酸根离子。我们利用这些分配来描述 BRCT 结构域在溶液中的二级结构和骨架动力学特征。突变布鲁氏菌 KKT4 BRCT 中参与磷酸盐离子结合的残基会导致生长缺陷,这证实了 BRCT 磷肽结合活性在体内的重要性。这些结果可能有助于未来的合理药物设计工作,以防治由内生寄生虫引起的疾病。
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NMR study of the structure and dynamics of the BRCT domain from the kinetochore protein KKT4

KKT4 is a multi-domain kinetochore protein specific to kinetoplastids, such as Trypanosoma brucei. It lacks significant sequence similarity to known kinetochore proteins in other eukaryotes. Our recent X-ray structure of the C-terminal region of KKT4 shows that it has a tandem BRCT (BRCA1 C Terminus) domain fold with a sulfate ion bound in a typical binding site for a phosphorylated serine or threonine. Here we present the 1H, 13C and 15N resonance assignments for the BRCT domain of KKT4 (KKT4463–645) from T. brucei. We show that the BRCT domain can bind phosphate ions in solution using residues involved in sulfate ion binding in the X-ray structure. We have used these assignments to characterise the secondary structure and backbone dynamics of the BRCT domain in solution. Mutating the residues involved in phosphate ion binding in T. brucei KKT4 BRCT results in growth defects confirming the importance of the BRCT phosphopeptide-binding activity in vivo. These results may facilitate rational drug design efforts in the future to combat diseases caused by kinetoplastid parasites.

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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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