Abstract：
Plasma membrane proteins (PMPs) play critical roles in a myriad of physiological and disease conditions. A unique subset of PMPs functions through interacting with each other in trans at the interface between two contacting cells. These trans-interacting PMPs (tiPMPs) include adhesion molecules and ligands/receptors that facilitate cell-cell contact and direct communication between cells. Among the tiPMPs, a significant number have apparent extracellular binding domains but remain orphans with no known binding partners. Identification of their potential binding partners is therefore important for the understanding of processes such as organismal development and immune cell activation. While a number of methods have been developed for the identification of protein binding partners in general, very few are applicable to tiPMPs, which interact in a two-dimensional fashion with low intrinsic binding affinities. In this review, we present the significance of tiPMP interactions, the challenges of identifying binding partners for tiPMPs, and the landscape of method development. We describe current avidity-based screening approaches for identifying novel tiPMP binding partners and discuss their advantages and limitations. We conclude by highlighting the importance of developing novel methods of identifying new tiPMP interactions for deciphering the complex protein interactome and developing targeted therapeutics for diseases.
摘要：
血浆膜蛋白（PMPs）在许多生理和疾病状况中起关键作用。PMP的独特子集通过在两个接触细胞之间的界面处彼此反式相互作用而起作用。这些反式相互作用PMPs(tiPMPs)包括粘附分子和促进细胞-细胞接触和细胞间直接通讯的配体/受体。在TIPMP中，相当多的人具有明显的细胞外结合结构域，但仍然是孤儿，没有已知的结合伴侣。因此,鉴定它们的潜在结合配偶体对于理解诸如生物体发育和免疫细胞活化的过程是重要的。虽然已经开发了许多方法来鉴定蛋白质结合配偶体，很少适用于TIPMP，它们以二维方式相互作用，具有低的内在结合亲和力。在这次审查中,我们提出了tiPMP相互作用的重要性，确定TIPMP的具有约束力的伙伴的挑战，以及方法发展的景观。我们描述了当前基于亲合力的筛选方法，用于鉴定新型tiPMP结合伴侣，并讨论了它们的优点和局限性。最后，我们强调了开发鉴定新的tiPMP相互作用的新方法的重要性，以破译复杂的蛋白质相互作用组和开发疾病的靶向治疗方法。
