EFFECTORS OF ORGANIZATION OF TRANSMEMBRANE PROTEINS

对构成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 在细胞内穿行细胞膜，也是需要的 澄清。在这个项目中，有两种蛋白质，乙酰胆碱受体 (AcChR)和线粒体基质蛋白天冬氨酸的前体 氨基转移酶(PmAAT)被用作模型以获得更好的理解 上述问题中的一部分。在第一种情况下，特别注意 特异性赖氨酸定量技术的研究进展 所有构成亚基序列中的残基到 膜的细胞质一侧，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 和特定的神经毒素和选定的抗突触抗体 (外部)方面也将进行，以及这样的效果 (远)细胞质暴露中的蛋白质-蛋白质相互作用 侧链赖氨酸残留物。在第二个蛋白质系统中，一种 前体作为一种分离的、可溶的、稳定的蛋白质提供了第一个 观察受控的前体-膜相互作用的机会 条件。因此，在pmAAT中，前序后果的作用 这种关于前体结构的研究，将通过抗体和多种方法进行评估 生物物理工具。

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.