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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The structure of carbonmonoxy neuroglobin reveals a heme-sliding mechanism for control of ligand affinity
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The structure of carbonmonoxy neuroglobin reveals a heme-sliding mechanism for control of ligand affinity

机译：碳单氧神经球蛋白的结构揭示了控制配体亲和力的血红素滑动机制

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Neuroglobin (Ngb), a globular heme protein expressed in the brain of vertebrates, binds oxygen reversibly, with an affinity comparable to myoglobin (Mb). Despite low sequence identity, the overall 3D fold of Ngb and Mb is very similar. Unlike in Mb, in Ngb the sixth coordination position of the heme iron is occupied by the distal histidine, in the absence of an exogenous ligand. Endogenous ligation has been proposed as a unique mechanism for affinity regulation and ligand discrimination in heme proteins. This peculiarity might be related to the still-unknown physiological function of Ngb. Here, we present the x-ray structure of CO-bound ferrous murine Ngb at 1.7 A and a comparison with the 1.5-A structure of ferric bis-histidine Ngb. We have also used Fourier transform IR spectroscopy of WT and mutant CO-ligated Ngb to examine structural heterogeneity in the active site. Upon CO binding, the distal histidine retains (by and large) its position, whereas the heme group slides deeper into a preformed crevice, thereby reshaping the large cavity (≈290 A~3) connecting the distal and proximal heme sides with the bulk. The heme relocation is accompanied by a significant decrease of structural disorder, especially of the EF loop, which may be the signal whereby Ngb communicates hypoxic conditions. This unexpected structural change unveils a heme-sliding mechanism of affinity control that may be of significance to understanding Ngb's role in the patho-physiology of the brain.
机译：神经球蛋白（Ngb）是在脊椎动物的大脑中表达的球形血红素蛋白，可逆地结合氧，其亲和力可与肌红蛋白（Mb）相媲美。尽管序列同一性较低，但Ngb和Mb的整体3D折叠非常相似。与Mb不同，在Ngb中，在没有外源配体的情况下，血红素铁的第六个配位位置被远端的组氨酸占据。已提出内源性连接作为血红蛋白中亲和力调节和配体识别的独特机制。这种特殊性可能与Ngb仍未知的生理功能有关。在这里，我们介绍了在1.7 A下与CO结合的亚铁鼠Ngb的X射线结构，以及与双组氨酸Ngb的1.5-A结构的比较。我们还使用了WT和突变CO连接的Ngb的傅里叶变换红外光谱来检查活性位点的结构异质性。一氧化碳结合后，远端组氨酸保留（大体上）其位置，而血红素基团更深地滑入预先形成的缝隙中，从而使连接远端和近端血红素侧与本体的大腔体重新塑形（≈290A〜3）。血红素的重新定位伴随着结构紊乱（尤其是EF环）的显着减少，这可能是Ngb传达缺氧状况的信号。这种意想不到的结构变化揭示了亲和力控制的血红素滑动机制，这可能对理解Ngb在大脑病理生理中的作用很重要。

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