EFFECTORS OF ORGANIZATION OF TRANSMEMBRANE PROTEINS

组成性膜蛋白的构象知之甚少， 膜脂对这些蛋白质的影响，或对那些必须 在细胞内运输中穿过膜，也需要 澄清。 在这个项目中，两种蛋白质，乙酰胆碱受体 （AcChR）和线粒体基质蛋白的前体天冬氨酸 氨基转移酶（pmAAT），被用作模型，以获得更好的理解 上述问题。 在第一种情况下，应特别注意 定量技术的发展，以指定特定的赖氨酰 所有组成型亚基的序列中的残基， 细胞膜的细胞质侧，这是一个在很大程度上未被探索的区域， 跨膜蛋白 AcChR之间接触点的表征 特异性神经毒素和抗突触神经毒素的抗体 （外部）方也将进行，以及这样的效果 蛋白质-蛋白质相互作用暴露的（远）细胞质 侧赖氨酰残基。 在第二种蛋白质系统中， 前体作为一种分离的、可溶的、稳定的蛋白质， 有机会在受控条件下观察吸附剂-膜相互作用 条件 因此，在pmAAT中， 例如对前体结构的影响，将通过抗体和各种 生物物理学工具。

The conformation of constitutive membrane proteins is poorly understood and the effect of membrane lipids on these proteins, or on those that must traverse membranes in intracellular traffic, is also in need of clarification. In this project, two proteins, the acetylcholine receptor (AcChR) and a precursor to a mitochondrial matrix protein, aspartate aminotransferase (pmAAT), are used as models to gain greater understanding of the above problems. In the first case, particular attention is paid to the development of quantitative techniques to assign specific lysyl residues in the sequence of all the constitutive subunits to the cytoplasmic side of the membrane, which is a region largely unexplored in transmembranous proteins. Characterization of contact points between AcChR and specific neurotoxins and selected antibodies against synaptic (exterior) side will also be carried out, as well as the effect of such protein-protein interactions in the exposure of the (distant) cytoplasmic side lysyl residues. iN the second protein system, the availability of a precursor as an isolated, soluble, stable protein provides the first opportunity to observe precursor-membrane interactions under controlled conditions. Thus, in pmAAT, the role of the presequence consequences of such on precursor structure, will be assessed by antibodies and a variety of biophysical tools.