Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 N Wolfe Street, Baltimore, MD 21205, USA.
Structure. 2011 Apr 13;19(4):503-14. doi: 10.1016/j.str.2011.01.017.
Fission yeast protein Sre1, the homolog of the mammalian sterol regulatory element-binding protein (SREBP), is a hypoxic transcription factor required for sterol homeostasis and low-oxygen growth. Nro1 regulates the stability of the N-terminal transcription factor domain of Sre1 (Sre1N) by inhibiting the action of the prolyl 4-hydroxylase-like Ofd1 in an oxygen-dependent manner. The crystal structure of Nro1 determined at 2.2 Å resolution shows an all-α-helical fold that can be divided into two domains: a small N-terminal domain, and a larger C-terminal HEAT-repeat domain. Follow-up studies showed that Nro1 defines a new class of nuclear import adaptor that functions both in Ofd1 nuclear localization and in the oxygen-dependent inhibition of Ofd1 to control the hypoxic response.
裂殖酵母蛋白 Sre1 是哺乳动物固醇调节元件结合蛋白 (SREBP) 的同源物，是一种低氧转录因子，对于固醇稳态和低氧生长是必需的。Nro1 通过抑制脯氨酰 4-羟化酶样 Ofd1 的作用来调节 Sre1（Sre1N）的 N 端转录因子结构域的稳定性，这种作用是依赖于氧的。Nro1 的晶体结构在 2.2 Å 分辨率下确定，显示出全α-螺旋折叠，可以分为两个结构域：一个小的 N 端结构域和一个较大的 C 端 HEAT-repeat 结构域。后续研究表明，Nro1 定义了一种新的核输入衔接子，它既能控制 Ofd1 的核定位，也能在依赖氧的情况下抑制 Ofd1，从而控制低氧反应。
