1H, 13C and 15N backbone resonance assignments of hepatocyte nuclear factor-1-beta (HNF1β) POUS and POUHD

IF 0.8 4区 生物学 Q4 BIOPHYSICS Biomolecular NMR Assignments Pub Date : 2024-03-07 DOI:10.1007/s12104-024-10168-4
Sayaka Hokazono, Eri Imagawa, Daishi Hirano, Takahisa Ikegami, Kimihiko Oishi, Tsuyoshi Konuma
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Abstract

Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor that plays a key role in the development and function of the liver, pancreas, and kidney. HNF1β plays a key role in early vertebrate development and the morphogenesis of these organs. In humans, heterozygous mutations in the HNF1B gene can result in organ dysplasia, making it the most common cause of developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. Pathogenic variants in the HNF1B gene are known to cause various diseases, including maturity-onset diabetes of the young and developmental renal diseases. This study presents the backbone resonance assignments of HNF1β POUS and POUHD domains, which are highly conserved domains required for the recognition of double-stranded DNA. Our data will be useful for NMR studies to verify the altered structures and functions of mutant HNF1B proteins that can induce developmental renal diseases, including renal cysts, renal malformations, and familial hypoplastic glomerular cystic kidney disease. This study will provide the structural basis for future studies to elucidate the molecular mechanisms underlying how mutations in HNF1β cause diseases.

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肝细胞核因子-1-β(HNF1β)POUS 和 POUHD 的 1H、13C 和 15N 主干共振分配。
肝细胞核因子 1β(HNF1β)是一种转录因子,在肝脏、胰腺和肾脏的发育和功能中起着关键作用。HNF1β 在脊椎动物的早期发育和这些器官的形态发生中起着关键作用。在人类中,HNF1B 基因的杂合子突变可导致器官发育不良,是导致肾脏发育疾病(包括肾囊肿、肾畸形和家族性肾小球发育不全囊性肾病)的最常见原因。已知 HNF1B 基因的致病变异可导致多种疾病,包括成熟期发病的青年糖尿病和发育性肾病。本研究展示了 HNF1β POUS 和 POUHD 结构域的骨架共振分配,这两个结构域是识别双链 DNA 所需的高度保守结构域。我们的数据将有助于核磁共振研究验证突变型 HNF1B 蛋白结构和功能的改变,这些突变型 HNF1B 蛋白可诱发肾脏发育疾病,包括肾囊肿、肾畸形和家族性肾小球发育不全囊性肾病。这项研究将为今后的研究提供结构基础,以阐明 HNF1β 突变如何导致疾病的分子机制。
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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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