Isolated or as a part of multidomain proteins, Sterol Carrier Protein 2 (SCP2) exhibits high affinity and broad specificity for different lipidic and hydrophobic compounds. A wealth of structural information on SCP2 domains in all forms of life is currently available; however, many aspects of its ligand binding activity are poorly understood. ylSCP2 is a well-characterized single domain SCP2 from the yeast Yarrowia lipolytica. Herein, we report the X-ray structure of unliganded ylSCP2 refined to 2.0 Å resolution. Comparison with the previously solved liganded ylSCP2 structure unveiled a novel mechanism for binding site occlusion. The liganded ylSCP2 binding site is a large cavity with a volume of more than 800 Å³. In unliganded ylSCP2 the binding site is reduced to about 140 Å³. The obliteration is caused by a swing movement of the C-terminal α helix 5 and a subtle compaction of helices 2–4. Previous pairwise comparisons were between homologous SCP2 domains with a uncertain binding status. The reported unliganded ylSCP2 structure allows for the first time a fully controlled comparative analysis of the conformational effects of ligand occupation dispelling several doubts regarding the architecture of SCP2 binding site.

分离或作为多域蛋白的一部分，甾醇载体蛋白 2 (SCP2) 对不同的脂质和疏水化合物表现出高亲和力和广泛的特异性。目前可以获得关于所有生命形式的 SCP2 域的大量结构信息；然而，对其配体结合活性的许多方面知之甚少。ylSCP2 是来自酵母解脂耶氏酵母的充分表征的单域 SCP2 。在此，我们报告了分辨率为 2.0 Å 的未配体 ylSCP2 的 X 射线结构。与之前解决的配体 ylSCP2 结构的比较揭示了结合位点封闭的新机制。配体的 ylSCP2 结合位点是一个体积超过 800 Å ³的大空腔。在未配体的 ylSCP2 中，结合位点减少到约 140 ų . 消失是由 C 端 α 螺旋 5 的摆动运动和螺旋 2-4 的微妙压实引起的。之前的成对比较是在具有不确定结合状态的同源 SCP2 域之间进行的。报道的未配体 ylSCP2 结构首次允许对配体占据的构象效应进行完全受控的比较分析，消除了对 SCP2 结合位点结构的一些怀疑。