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在转录调节器HcpRR中的全长结构和血红蛋白结合

Benjamin Ross Belvin¹, Faik N Musayev^2,3, Carlos R Escalante⁴

¹The Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, Virginia 23298, United States.

|January 1, 2026

概括

Porphyromonas gingivalis HcpR 是一个转录调节器,它与heme结合. 研究人员阐明了它的结构,揭示了一个对血红素结合至关重要的口袋,并在对氧化的反应中调节基因表达的功能.

科学领域:

微生物学微生物学
结构生物学结构生物学
分子生物学分子生物学

背景情况:

HcpR是一种依赖于血红素的转录调节剂,存在于格拉姆阴性无氧细菌中.
在 Porphyromonas gingivalis 中,HcpR 调节对像氧化 (NO) 等反应性物种的反应.
血与HcpR结合的机制以前是未知的.

研究的目的:

为了确定P. gingivalis HcpR. 的结构.
阐明血红素与HcpR结合的分子机制.
为了确定参与HcpR功能和血红蛋白协调的关键残留物.

主要方法:

在P. gingivalis HcpR.的X射线晶体 (2.3 Å分辨率) 的X射线.
与CRP/FNR家族监管器进行生物信息比较.
分子对接研究,以预测血红素结合部位.
在体内补充和突变发生的测试.
用净化复合HcpR.R.进行血红蛋白结合研究.

主要成果:

2.3 Å 结构揭示了域间相互作用,在 N-终端传感域中形成了一个疏水口袋.
对比表明HcpR调节可能与其他CRP/FNR家族成员有所不同.
通过对接,在口袋内确定了一个可谓的血结合部位.
突变和补充证实了Methionine 68 (Met68) 对于转录激活至关重要.
血红素结合研究验证了Met68在血红素结合和协调中的关键作用.

结论:

这项研究介绍了P. gingivalis HcpR的结构,揭示了一个独特的血结合口袋.
氨酸68被确定为结合和HcpR介导的转录调节的关键残留物.
这些发现提供了对HcpR家族调节者的独特分子机制的洞察.

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