Stadtmueller Beth M, Yang Zhongyu, Huey-Tubman Kathryn E, Roberts-Mataric Helena, Hubbell Wayne L, Bjorkman Pamela J
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125;
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095; and Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA 90095.
J Immunol. 2016 Aug 15;197(4):1408-14. doi: 10.4049/jimmunol.1600463. Epub 2016 Jul 13.
The polymeric Ig receptor (pIgR) transports polymeric Abs across epithelia to the mucosa, where proteolytic cleavage releases the ectodomain (secretory component [SC]) as an integral component of secretory Abs, or as an unliganded protein that can mediate interactions with bacteria. SC is conserved among vertebrates, but domain organization is variable: mammalian SC has five domains (D1-D5), whereas avian, amphibian, and reptilian SC lack the D2 domain, and fish SC lacks domains D2-D4. In this study, we used double electron-electron resonance spectroscopy and surface plasmon resonance binding studies to characterize the structure, dynamics, and ligand binding properties of avian SC, avian SC domain variants, and a human SC (hSC) variant lacking the D2 domain. These experiments demonstrated that, unlike hSC, which adopts a compact or "closed" domain arrangement, unliganded avian SC is flexible and exists in both closed and open states, suggesting that the mammalian SC D2 domain stabilizes the closed conformation observed for hSC D1-D5. Experiments also demonstrated that avian and mammalian pIgR share related, but distinct, mechanisms of ligand binding. Together, our data reveal differences in the molecular recognition mechanisms associated with evolutionary changes in the pIgR protein.
多聚免疫球蛋白受体（pIgR）将多聚抗体转运穿过上皮细胞至黏膜，在黏膜处蛋白水解切割释放出胞外结构域（分泌成分[SC]），作为分泌性抗体的一个组成部分，或者作为一种可介导与细菌相互作用的未结合配体的蛋白质。SC在脊椎动物中是保守的，但结构域组织是可变的：哺乳动物的SC有五个结构域（D1 - D5），而鸟类、两栖类和爬行类的SC缺少D2结构域，鱼类的SC缺少D2 - D4结构域。在本研究中，我们使用双电子 - 电子共振光谱和表面等离子体共振结合研究来表征鸟类SC、鸟类SC结构域变体以及缺少D2结构域的人类SC（hSC）变体的结构、动力学和配体结合特性。这些实验表明，与采用紧密或“封闭”结构域排列的hSC不同，未结合配体的鸟类SC是灵活的，存在封闭和开放两种状态，这表明哺乳动物的SC D2结构域稳定了hSC D1 - D5所观察到的封闭构象。实验还表明，鸟类和哺乳动物的pIgR具有相关但不同的配体结合机制。总之，我们的数据揭示了与pIgR蛋白进化变化相关的分子识别机制的差异。
