巴塞罗那自治大学(UAB)的研究人员发现，某些蛋白质即使折叠正确，但仍然能够导致多种蛋白质构象病，如肌萎缩性侧索硬化症(amyotrophic lateral sclerosis)，家族性淀粉样心肌病(familial amyloidotic cardiomyopathy)等。
研究人员对这些蛋白质各个亚基的三维结构进行分析，最终发现了答案所在——这些蛋白质通常是由两个或两个以上的亚基构成，即使蛋白质折叠正确，如果各亚基在组合过程中发生突变，同样能使该蛋白质成为毒性大分子淀粉体纤维(amyloid fibrils)。这项研究发表在近期的PLoS Computational Biology。
蛋白质聚集和错误折叠与一些遗传性或自发性的构象类疾病相关。蛋白质聚集成球状蛋白将导致肝脏，心脏，肾脏和神经疾病。研究人员通过计算机分析，发现在非病理条件下，与构象疾病相关的球状蛋白是成对连接到其他蛋白或亚基复合体中。在连接过程中，蛋白易聚集区域(aggregation-prone regions)相互覆盖，这样就防止易聚集区外露引起蛋白质聚集。但研究人员发现，若连接的区域发生突变，将阻止连接发生，并形成毒性大分子聚集物。
因此，为了阻止蛋白质之间的解离，研究人员打算引入一种能使蛋白质之间加强联系的基因突变，并开发一种特异性阻断已解离区域相互聚集的大分子。（生物谷Bioon.com）
生物谷推荐原始出处：
PLoS Comput Biol 5(8): e1000476. doi:10.1371/journal.pcbi.1000476
Amyloidogenic Regions and Interaction Surfaces Overlap in Globular Proteins Related to Conformational Diseases
Virginia Castillo, Salvador Ventura*
Departament de Bioquímica i Biologia Molecular and Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Barcelona, Spain
Protein aggregation underlies a wide range of human disorders. The polypeptides involved in these pathologies might be intrinsically unstructured or display a defined 3D-structure. Little is known about how globular proteins aggregate into toxic assemblies under physiological conditions, where they display an initially folded conformation. Protein aggregation is, however, always initiated by the establishment of anomalous protein-protein interactions. Therefore, in the present work, we have explored the extent to which protein interaction surfaces and aggregation-prone regions overlap in globular proteins associated with conformational diseases. Computational analysis of the native complexes formed by these proteins shows that aggregation-prone regions do frequently overlap with protein interfaces. The spatial coincidence of interaction sites and aggregating regions suggests that the formation of functional complexes and the aggregation of their individual subunits might compete in the cell. Accordingly, single mutations affecting complex interface or stability usually result in the formation of toxic aggregates. It is suggested that the stabilization of existing interfaces in multimeric proteins or the formation of new complexes in monomeric polypeptides might become effective strategies to prevent disease-linked aggregation of globular proteins.
