Ben-Shem Adam, Fass Deborah, Bibi Eitan
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):462-6. doi: 10.1073/pnas.0609773104. Epub 2006 Dec 26.
Intramembrane proteases catalyze peptide bond cleavage of integral membrane protein substrates. This activity is crucial for many biological and pathological processes. Rhomboids are evolutionarily widespread intramembrane serine proteases. Here, we present the 2.3-A-resolution crystal structure of a rhomboid from Escherichia coli. The enzyme has six transmembrane helices, five of which surround a short TM4, which starts deep within the membrane at the catalytic serine residue. Thus, the catalytic serine is in an externally exposed cavity, which provides a hydrophilic environment for proteolysis. Our results reveal a mechanism to enable water-dependent catalysis at the depth of the hydrophobic milieu of the membrane and suggest how substrates gain access to the sequestered rhomboid active site.
膜内蛋白酶催化整合膜蛋白底物的肽键裂解。这种活性对许多生物学和病理学过程至关重要。类菱形蛋白酶是在进化上广泛存在的膜内丝氨酸蛋白酶。在此，我们展示了来自大肠杆菌的一种类菱形蛋白酶的2.3埃分辨率晶体结构。该酶有六个跨膜螺旋，其中五个围绕着短的TM4，TM4在膜内深处从催化丝氨酸残基处开始。因此，催化丝氨酸位于一个外部暴露的腔内，该腔为蛋白水解提供了一个亲水环境。我们的结果揭示了一种在膜的疏水环境深处实现水依赖催化的机制，并表明底物如何进入被隔离的类菱形蛋白酶活性位点。
