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.
摘要：
肝细胞核因子1β（HNF1β）是一种转录因子，在肝脏的发育和功能中起着关键作用，胰腺,还有肾.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基因的杂合突变可导致器官发育不良，使其成为发展性肾脏疾病的最常见原因，包括肾囊肿,肾畸形,家族性增生性肾小球囊性肾病。已知HNF1B基因中的致病变体会导致各种疾病，包括年轻人的成熟型糖尿病和发育性肾脏疾病。本研究提出了HNF1βPOUS和POUHD结构域的主链共振分配，它们是识别双链DNA所需的高度保守的结构域。我们的数据将有助于NMR研究，以验证突变的HNF1B蛋白的结构和功能的改变，这些蛋白可以诱导发育性肾脏疾病，包括肾囊肿,肾畸形,家族性增生性肾小球囊性肾病。这项研究将为未来研究提供结构基础，以阐明HNF1β突变如何引起疾病的分子机制。
