Chuartzman Silvia G, Nevo Reinat, Waichman Sharon, Shental Dalit, Piehler Jacob, Levy Yaakov, Reich Ziv, Kapon Ruti
Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
Department of Biology, University of Osnabrück, Osnabrück, Germany.
PLoS One. 2017 Apr 12;12(4):e0175413. doi: 10.1371/journal.pone.0175413. eCollection 2017.
Differential signaling of the type I interferon receptor (IFNAR) has been correlated with the ability of its subunit, IFNAR1, to differentially recognize a large spectrum of different ligands, which involves intricate conformational re-arrangements of multiple interacting domains. To shed light onto the structural determinants governing ligand recognition, we compared the force-induced unfolding of the IFNAR1 ectodomain when bound to interferon and when free, using the atomic force microscope and steered molecular dynamics simulations. Unexpectedly, we find that IFNAR1 is easier to mechanically unfold when bound to interferon than when free. Analysis of the structures indicated that the origin of the reduction in unfolding forces is a conformational change in IFNAR1 induced by ligand binding.
I型干扰素受体（IFNAR）的差异信号传导与其亚基IFNAR1鉴别多种不同配体的能力相关，这涉及多个相互作用结构域复杂的构象重排。为了阐明决定配体识别的结构因素，我们使用原子力显微镜和引导分子动力学模拟，比较了结合干扰素时和游离状态下IFNAR1胞外域的力诱导去折叠情况。出乎意料的是，我们发现与游离状态相比，IFNAR1在结合干扰素时更容易发生机械去折叠。对结构的分析表明，去折叠力降低的原因是配体结合诱导IFNAR1发生了构象变化。
