Department of Biological Sciences, University of Essex, Colchester, Essex, UK.
Biochem J. 2011 Mar 15;434(3):483-92. doi: 10.1042/BJ20101136.
Cytoglobin is a recently discovered hexa-co-ordinate haemoglobin that does not appear to function as a classical oxygen-binding protein. Its function is unknown and studies on the effects of changes in its expression have not decisively determined its role within the cell. In the present paper, we report that the protein is transformed from hexa-co-ordinate to penta-co-ordinate on binding a lipid molecule. This transformation occurs with the ferric oxidation state of the protein, but not the ferrous state, indicating that this process only occurs under an oxidative environment and may thus be related to redox-linked cell signalling mechanisms. Oleate binds to the protein in a 1:1 stoichiometry and with high affinity (K(d)=0.7 μM); however, stopped-flow kinetic measurements yield a K(d) value of 110 μM. The discrepancy between these K(d) values may be rationalized by recognizing that cytoglobin is a disulfide-linked dimer and invoking co-operativity in oleate binding. The lipid-induced transformation of cytoglobin from hexa-co-ordinate to penta-co-ordinate does not occur with similar hexa-co-ordinate haemoglobins such as neuroglobin, and therefore appears to be a unique property of cytoglobin among the haemoglobin superfamily. The lipid-derived transformation may explain why cytoglobin has enhanced peroxidatic activity, converting lipids into various oxidized products, a property virtually absent from neuroglobin and much decreased in myoglobin. We propose that the binding of ferric cytoglobin to lipids and their subsequent transformation may be integral to the physiological function of cytoglobin, generating cell signalling lipid molecules under an oxidative environment.
细胞球蛋白是一种最近发现的六配位血红蛋白，它似乎不具有作为经典氧结合蛋白的功能。其功能未知，对其表达变化影响的研究尚未确定其在细胞内的作用。在本文中，我们报告说，该蛋白在结合脂质分子时从六配位转变为五配位。这种转变发生在蛋白质的高铁氧化态，而不是亚铁态，表明这个过程仅在氧化环境下发生，可能与氧化还原相关的细胞信号转导机制有关。油酸盐以 1:1 的化学计量比和高亲和力（K(d)=0.7 μM）结合到蛋白上；然而，停流动力学测量得出的 K(d)值为 110 μM。这些 K(d)值之间的差异可以通过认识到细胞球蛋白是一个二硫键连接的二聚体，并推断出油酸盐结合的协同作用来合理化。脂质诱导的细胞球蛋白从六配位到五配位的转变不会发生在类似的六配位血红蛋白如神经球蛋白中，因此似乎是血红蛋白超家族中细胞球蛋白的独特性质。脂质衍生的转变可能解释了为什么细胞球蛋白具有增强的过氧化物酶活性，将脂质转化为各种氧化产物，而神经球蛋白几乎没有这种活性，肌红蛋白的活性大大降低。我们提出，铁细胞球蛋白与脂质的结合及其随后的转变可能是细胞球蛋白生理功能的一个组成部分，在氧化环境下产生细胞信号脂质分子。
