Qi Shiqian, O'Hayre Morgan, Gutkind J Silvio, Hurley James H
Department of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California, 94720.
Protein Sci. 2014 Dec;23(12):1708-16. doi: 10.1002/pro.2549. Epub 2014 Sep 26.
ARRDC3 is one of six known human α-arrestins, and has been implicated in the downregulation of the β2-adrenergic receptor (β2AR). ARRDC3 consists of a two-lobed arrestin fold and a C-terminal tail containing two PPYX motifs. In the current model for receptor downregulation by ARRDC3, the arrestin fold portion is thought to bind the receptor, while the PPXY motifs recruit ubiquitin ligases of the NEDD4 family. Here we report the crystal structures of the N-terminal lobe of human ARRDC3 in two conformations, at 1.73 and 2.8 Å resolution, respectively. The structures reveal a large electropositive region that is capable of binding phosphate ions of crystallization. Residues within the basic patch were shown to be important for binding to β2AR, similar to the situation with β-arrestins. This highlights potential parallels in receptor recognition between α- and β-arrestins.
ARRDC3是已知的六种人类α-抑制蛋白之一，与β2-肾上腺素能受体（β2AR）的下调有关。ARRDC3由一个两叶的抑制蛋白折叠结构和一个包含两个PPYX基序的C末端尾巴组成。在目前关于ARRDC3介导受体下调的模型中，抑制蛋白折叠部分被认为与受体结合，而PPXY基序则招募NEDD4家族的泛素连接酶。在此，我们报告了人ARRDC3 N末端叶的两种构象的晶体结构，分辨率分别为1.73 Å和2.8 Å。这些结构揭示了一个能够结合结晶磷酸盐离子的大的正电区域。碱性区域内的残基被证明对于与β2AR的结合很重要，这与β-抑制蛋白的情况类似。这突出了α-抑制蛋白和β-抑制蛋白在受体识别方面潜在的相似之处。
