Departamento de Física Macromolecular, Instituto de Estructura de la Materia, Madrid, Spain.
Eur Biophys J. 2011 Jul;40(7):835-42. doi: 10.1007/s00249-011-0699-y. Epub 2011 Apr 8.
ErbB2 and ErbB3 receptors belong to the epidermal growth factor receptor family. The members of this family are able to form homo- and heterodimers that trigger diverse downstream signalling concerned to multiple cellular events. In the absence of a ligand, ErbB3 adopts a characteristic tethered conformation, which differs from ErbB2 extended conformation. In this work, transmission electron microscopy (TEM) and dynamic light scattering (DLS) have been used to characterize the conformational features and the size of ErBb2 and ErbB3 receptors. Two main objectives are presented. The first one is to evaluate the use of TEM as a tool for structural studies for this family of receptors. The low molecular weight of these proteins represents a challenging purpose for TEM studies. The other one is to search for a relationship between the results obtained by TEM and those obtained for the hydrodynamic size measured by DLS. This comparison has allowed us to identify the conformational differences of the receptors and to anticipate the use of these experimental techniques for the study of the ligand activated heterodimerization, a process related to a significant number of human malignancies.
ErbB2 和 ErbB3 受体属于表皮生长因子受体家族。这个家族的成员能够形成同型和异型二聚体，触发与多种细胞事件相关的不同下游信号转导。在没有配体的情况下，ErbB3 采用一种特征性的束缚构象，与 ErbB2 的伸展构象不同。在这项工作中，我们使用透射电子显微镜（TEM）和动态光散射（DLS）来表征 ErBb2 和 ErbB3 受体的构象特征和大小。介绍了两个主要目标。第一个目标是评估 TEM 作为该受体家族结构研究工具的使用。这些蛋白质的低分子量代表了 TEM 研究的一个具有挑战性的目的。另一个目标是寻找 TEM 获得的结果与 DLS 测量的流体力学大小之间的关系。这种比较使我们能够识别受体的构象差异，并预测这些实验技术在研究与大量人类恶性肿瘤相关的配体激活异二聚化过程中的应用。
