UNC119 是感觉神经元中 G 蛋白运输所必需的。
UNC119 is required for G protein trafficking in sensory neurons.
机构信息
Department of Ophthalmology, University of Utah Health Science Center, Salt Lake City, Utah, USA.
出版信息
Nat Neurosci. 2011 Jun 5;14(7):874-80. doi: 10.1038/nn.2835.
Abstract
UNC119 is widely expressed among vertebrates and other phyla. We found that UNC119 recognized the acylated N terminus of the rod photoreceptor transducin α (Tα) subunit and Caenorhabditis elegans G proteins ODR-3 and GPA-13. The crystal structure of human UNC119 at 1.95-Å resolution revealed an immunoglobulin-like β-sandwich fold. Pulldowns and isothermal titration calorimetry revealed a tight interaction between UNC119 and acylated Gα peptides. The structure of co-crystals of UNC119 with an acylated Tα N-terminal peptide at 2.0 Å revealed that the lipid chain is buried deeply into UNC119's hydrophobic cavity. UNC119 bound Tα-GTP, inhibiting its GTPase activity, thereby providing a stable UNC119-Tα-GTP complex capable of diffusing from the inner segment back to the outer segment after light-induced translocation. UNC119 deletion in both mouse and C. elegans led to G protein mislocalization. Thus, UNC119 is a Gα subunit cofactor essential for G protein trafficking in sensory cilia.
摘要
UNC119 在脊椎动物和其他门中广泛表达。我们发现 UNC119 识别 rod 光感受器转导蛋白α (Tα) 亚基和秀丽隐杆线虫 G 蛋白 ODR-3 和 GPA-13 的酰化 N 末端。人 UNC119 的晶体结构分辨率为 1.95-Å，呈现免疫球蛋白样β-sandwich 折叠。下拉和等温热滴定法揭示了 UNC119 和酰化 Gα 肽之间的紧密相互作用。UNC119 与酰化 Tα N 端肽的共晶体结构揭示了脂质链深深地埋藏在 UNC119 的疏水性腔中。UNC119 结合 Tα-GTP，抑制其 GTPase 活性，从而提供了一种稳定的 UNC119-Tα-GTP 复合物，能够在光诱导易位后从内节扩散回外节。在小鼠和秀丽隐杆线虫中 UNC119 的缺失导致 G 蛋白定位错误。因此，UNC119 是一种 Gα 亚基共因子，对于感觉纤毛中的 G 蛋白运输至关重要。
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