Diao Jianbo, Zhang Ying, Huibregtse Jon M, Zhou Daoguo, Chen Jue
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Nat Struct Mol Biol. 2008 Jan;15(1):65-70. doi: 10.1038/nsmb1346. Epub 2007 Dec 9.
Bacterial pathogens deliver virulence proteins into host cells to facilitate entry and survival. Salmonella SopA functions as an E3 ligase to manipulate the host proinflammatory response. Here we report the crystal structure of SopA in two conformations. Although it has little sequence similarity to eukaryotic HECT-domain E3s, the C-terminal half of SopA has a bilobal architecture that is reminiscent of the N- and C-lobe arrangement of HECT domains. The SopA structure also contains a putative substrate-binding domain located near the E2-binding site. The two structures of SopA differ in the relative orientations of the C lobe, indicating that SopA possesses the conformational flexibility essential for HECT E3 function. These results suggest that SopA is a unique HECT E3 ligase evolved from the coevolutionary selective pressure at the bacterium-host interface.
细菌病原体将毒力蛋白输送到宿主细胞中，以促进其进入和存活。沙门氏菌SopA作为一种E3连接酶，可操纵宿主的促炎反应。在此，我们报告了处于两种构象的SopA的晶体结构。尽管SopA与真核HECT结构域E3几乎没有序列相似性，但其C端的后半部分具有双叶结构，这让人联想到HECT结构域的N叶和C叶排列。SopA结构还包含一个位于E2结合位点附近的假定底物结合结构域。SopA的两种结构在C叶的相对取向上有所不同，这表明SopA具有HECT E3功能所必需的构象灵活性。这些结果表明，SopA是一种独特的HECT E3连接酶，是在细菌-宿主界面的共同进化选择压力下进化而来的。
