Thielmann Yvonne, Weiergräber Oliver H, Mohrlüder Jeannine, Willbold Dieter
Institut für Strukturbiologie und Biophysik 3 (Strukturbiochemie), Forschungszentrum Jülich, Jülich, Germany.
Mol Biosyst. 2009 Jun;5(6):575-9. doi: 10.1039/b900425d. Epub 2009 Apr 9.
The GABA(A) receptor-associated protein (GABARAP) plays an important role in intracellular trafficking of several proteins. It undergoes a C-terminal lipidation process that enables anchoring in the cytosolic leaflet of cellular membranes. While the three-dimensional structure of GABARAP itself has been determined, structural investigation of complexes with its interaction partners has just commenced. Studies with indole derivatives revealed that GABARAP features two hydrophobic binding sites (hp1 and hp2). These also play an essential role in complex formation with the native ligand calreticulin. Furthermore, a model of hexameric N-ethylmaleimide-sensitive factor (NSF) suggests that binding of GABARAP to this molecular machine may involve a similar site. Since hp1 and hp2 are highly conserved throughout the GABARAP family, the relevance of the structural data presented here is likely to extend to GABARAP homologues.
γ-氨基丁酸A型（GABA(A)）受体相关蛋白（GABARAP）在多种蛋白质的细胞内运输中发挥重要作用。它会经历一个C末端脂化过程，从而能够锚定在细胞膜的胞质小叶中。虽然GABARAP自身的三维结构已经确定，但对其与相互作用伙伴形成的复合物的结构研究才刚刚开始。对吲哚衍生物的研究表明，GABARAP具有两个疏水结合位点（hp1和hp2）。这些位点在与天然配体钙网蛋白形成复合物的过程中也起着至关重要的作用。此外，六聚体N-乙基马来酰亚胺敏感因子（NSF）的模型表明，GABARAP与这种分子机器的结合可能涉及类似的位点。由于hp1和hp2在整个GABARAP家族中高度保守，此处呈现的结构数据的相关性可能会扩展到GABARAP同源物。
