Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
IUBMB Life. 2011 Mar;63(3):206-13. doi: 10.1002/iub.444.
Neuroglobin (Ngb) is a heme protein, highly conserved along evolution, predominantly found in the nervous system. It is upregulated by hypoxia and ischemia and may have a neuroprotective role under hypoxic stress. Although many other roles have been proposed, the physiological function is still unclear. Antarctic icefishes lack hemoglobin and some species also lack myoglobin, but all have Ngb and thus may help the elucidation of Ngb function. We present the first theoretically derived structure of fish Ngb and describe its behavior using molecular dynamics simulations. Specifically, we sequenced and analyzed Ngbs from a colorless-blooded Antarctic icefish species Chaenocephalus aceratus and a related red-blooded species (Dissostichus mawsoni). Both fish Ngbs are 6-coordinated but have some peculiarities that differentiate them from mammalian counterparts: they have extensions in the N and C termini that can interact with the EF loop, and a gap in the alignment that changes the CD-region structure/dynamics that has been found to play a key role in human neuroglobin. Our results suggest that a single mutation between both fish Ngbs is responsible for significant difference in the behavior of the proteins. The functional role of these characteristics is discussed.
神经球蛋白（Ngb）是一种血红素蛋白，在进化过程中高度保守，主要存在于神经系统中。它可被缺氧和缺血诱导表达，在缺氧应激下可能具有神经保护作用。尽管已经提出了许多其他作用，但生理功能仍不清楚。南极冰鱼缺乏血红蛋白，有些物种也缺乏肌红蛋白，但它们都具有 Ngb，因此可能有助于阐明 Ngb 的功能。我们提出了鱼类 Ngb 的第一个理论推导结构，并使用分子动力学模拟描述了其行为。具体来说，我们对一种无色血液的南极冰鱼物种 Chaenocephalus aceratus 和一种相关的红血鱼物种（Dissostichus mawsoni）的 Ngbs 进行了测序和分析。两种鱼类的 Ngbs 都是 6 配位的，但具有一些与哺乳动物对应物不同的特征：它们在 N 和 C 末端有延伸，可以与 EF 环相互作用，并且在对齐中存在一个缺口，这改变了 CD 区域的结构/动力学，在人类神经球蛋白中发现该结构/动力学起着关键作用。我们的结果表明，两种鱼类 Ngbs 之间的单个突变导致蛋白质行为的显著差异。讨论了这些特征的功能作用。
