Wu Zhuoru, Yan Nieng, Feng Liang, Oberstein Adam, Yan Hanchi, Baker Rosanna P, Gu Lichuan, Jeffrey Philip D, Urban Sinisa, Shi Yigong
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA.
Nat Struct Mol Biol. 2006 Dec;13(12):1084-91. doi: 10.1038/nsmb1179. Epub 2006 Nov 10.
Intramembrane proteolysis regulates diverse biological processes. Cleavage of substrate peptide bonds within the membrane bilayer is catalyzed by integral membrane proteases. Here we report the crystal structure of the transmembrane core domain of GlpG, a rhomboid-family intramembrane serine protease from Escherichia coli. The protein contains six transmembrane helices, with the catalytic Ser201 located at the N terminus of helix alpha4 approximately 10 A below the membrane surface. Access to water molecules is provided by a central cavity that opens to the extracellular region and converges on Ser201. One of the two GlpG molecules in the asymmetric unit has an open conformation at the active site, with the transmembrane helix alpha5 bent away from the rest of the molecule. Structural analysis suggests that substrate entry to the active site is probably gated by the movement of helix alpha5.
膜内蛋白水解作用调节多种生物学过程。膜双层内底物肽键的切割由整合膜蛋白酶催化。在此，我们报道了来自大肠杆菌的菱形家族膜内丝氨酸蛋白酶GlpG跨膜核心结构域的晶体结构。该蛋白包含六个跨膜螺旋，催化性丝氨酸201位于α4螺旋的N端，在膜表面下方约10埃处。一个通向细胞外区域并汇聚于丝氨酸201的中央腔为水分子提供了通道。不对称单元中的两个GlpG分子之一在活性位点具有开放构象，跨膜螺旋α5远离分子的其余部分弯曲。结构分析表明，底物进入活性位点可能由α5螺旋的移动控制。
