NMR structure reveals intramolecular regulation mechanism for pheromone binding and release
NMR structure reveals intramolecular regulation mechanism for pheromone binding and release
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DOI：
10.1073/pnas.251532998
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发表时间：
2001-12-04
影响因子：
11.1
通讯作者：
Wüthrich, K
中科院分区：
文献类型：
--
作者：
Horst, R;Damberger, F;Wüthrich, K
气味物质由小的疏水分子传递，这些分子穿过围绕嗅觉神经元树突的水性感器淋巴，以刺激嗅觉受体。在昆虫中，信息素（一类特殊的气味物质）的运输由信息素结合蛋白（PBPs）介导，这些蛋白在感器淋巴中浓度很高。家蚕（Bombyx mori）的信息素结合蛋白（BmPBP）在pH 4.5时存在的形式BmPBP(A)和pH 6.5时存在的形式BmPBP(B)之间经历一种依赖pH的构象转变。在此，我们描述了BmPBP(A)的核磁共振结构，它由七个α -螺旋紧密排列组成，这些螺旋由明确界定的肽段连接，并通过三个二硫键连接在一起。在BmPBP - 信息素复合物的晶体结构中形成配体结合位点的四个α -螺旋支架在BmPBP(A)中得以保留。C末端的十二肽段在信息素复合物中呈伸展构象且位于蛋白质表面，在未结合配体的BmPBP(A)核心的信息素结合位点处形成一个规则的螺旋α(7)。因为其他人的研究表明，膜表面附近的pH值相对于大量的感器淋巴有所降低，所以BmPBP依赖pH的构象转变提示了一种蛋白质功能分子内调节的新的生理机制，α7的形成触发信息素从BmPBP释放到膜上的受体。
Odorants are transmitted by small hydrophobic molecules that cross the aqueous sensillar lymph surrounding the dendrites of the olfactory neurons to stimulate the olfactory receptors. In insects, the transport of pheromones, which are a special class of odorants, is mediated by pheromone-binding proteins (PBPs), which occur at high concentrations in the sensillar lymph. The PBP from the silk moth Bombyx mori (BmPBP) undergoes a pH-dependent conformational transition between the forms BmPBP(A) present at pH 4.5 and BmPBP(B) present at pH 6.5. Here, we describe the NMR structure of BmPBPA, which consists of a tightly packed arrangement of seven alpha -helices linked by well defined peptide segments and knitted together by three disulfide bridges. A scaffold of four alpha -helices that forms the ligand binding site in the crystal structure of a BmPBP-pheromone complex is preserved in BMPBPA. The C-terminal dodecapeptide segment, which is in an extended conformation and located on the protein surface in the pheromone complex, forms a regular helix, alpha (7), which is located in the pheromone-binding site in the core of the unliganded BmPBP(A). Because investigations by others indicate that the pH value near the membrane surface is reduced with respect to the bulk sensillar lymph, the pH-dependent conformational transition of BmPBP suggests a novel physiological mechanism of intramolecular regulation of protein function, with the formation of alpha7 triggering the release of the pheromone from BmPBP to the membrane-standing receptor.