Smith Paul C, Firestein Stuart, Hunt John F
Department of Biological Sciences, 702A Fairchild Center, MC 2434, Columbia University, New York, NY 10027, USA
J Mol Biol. 2002 Jun 7;319(3):807-21. doi: 10.1016/S0022-2836(02)00242-5.
Olfactory marker protein (OMP) is a highly expressed and phylogenetically conserved cytoplasmic protein of unknown function found almost exclusively in mature olfactory sensory neurons. Electrophysiological studies of olfactory epithelia in OMP knock-out mice show strongly retarded recovery following odorant stimulation leading to an impaired response to pulsed odor stimulation. Although these studies show that OMP is a modulator of the olfactory signal-transduction cascade, its biochemical role is not established. In order to facilitate further studies on the molecular function of OMP, its crystal structure has been determined at 2.3 A resolution using multiwavelength anomalous diffraction experiments on selenium-labeled protein. OMP is observed to form a modified beta-clamshell structure with eight antiparallel beta-strands. While OMP has no significant sequence homology to proteins of known structure, it has a similar fold to a domain found in a variety of existing structures, including in a large family of viral capsid proteins. The surface of OMP is mostly convex and lacking obvious small molecule binding sites, suggesting that it is more likely to be involved in modulating protein-protein interaction than in interacting with small molecule ligands. Three highly conserved regions have been identified as leading candidates for protein-protein interaction sites in OMP. One of these sites represents a loop known to mediate ligand interactions in the structurally homologous EphB2 receptor ligand-binding domain. This site is partially buried in the crystal structure but fully exposed in the NMR solution structure of OMP due to a change in the orientation of an alpha-helix that projects outward from the structurally invariant beta-clamshell core. Gating of this conformational change by molecular interactions in the signal-transduction cascade could be used to control access to OMP's equivalent of the EphB2 ligand-interaction loop, thereby allowing OMP to function as a molecular switch.
嗅觉标记蛋白（OMP）是一种在成熟嗅觉感觉神经元中几乎唯一发现的、功能未知的高表达且系统发育保守的细胞质蛋白。对OMP基因敲除小鼠嗅觉上皮的电生理研究表明，气味刺激后恢复强烈延迟，导致对脉冲气味刺激的反应受损。尽管这些研究表明OMP是嗅觉信号转导级联的调节剂，但其生化作用尚未确定。为了便于进一步研究OMP的分子功能，已使用对硒标记蛋白的多波长反常衍射实验，以2.3埃的分辨率确定了其晶体结构。观察到OMP形成了一个具有八条反平行β链的修饰β-蛤壳结构。虽然OMP与已知结构的蛋白质没有显著的序列同源性，但它与在各种现有结构中发现的一个结构域具有相似的折叠，包括在一大类病毒衣壳蛋白中。OMP的表面大多是凸起的，缺乏明显的小分子结合位点，这表明它更有可能参与调节蛋白质-蛋白质相互作用，而不是与小分子配体相互作用。已确定三个高度保守的区域是OMP中蛋白质-蛋白质相互作用位点的主要候选区域。其中一个位点代表一个已知在结构同源的EphB2受体配体结合结构域中介导配体相互作用的环。该位点在晶体结构中部分被掩埋，但在OMP的核磁共振溶液结构中完全暴露，这是由于从结构不变的β-蛤壳核心向外突出的α-螺旋方向发生了变化。信号转导级联中的分子相互作用对这种构象变化的门控可用于控制对OMP中相当于EphB2配体相互作用环的区域的访问，从而使OMP能够作为分子开关发挥作用。
