Structural basis for intramembrane proteolysis by rhomboid serine proteases
Structural basis for intramembrane proteolysis by rhomboid serine proteases
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DOI：
10.1073/pnas.0609773104
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发表时间：
2007-01-09
影响因子：
11.1
通讯作者：
Bibi, Eitan
中科院分区：
文献类型：
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作者：
Ben-Shem, Adam;Fass, Deborah;Bibi, Eitan
膜内蛋白酶催化整合膜蛋白底物的肽键裂解。这种活性对于许多生物和病理过程至关重要。菱形体是进化上广泛分布的膜内丝氨酸蛋白酶。在这里，我们提出了2.3埃分辨率的晶体结构的菱形从大肠杆菌。该酶有六个跨膜螺旋，其中五个围绕着一个短的TM4，它在膜内的催化丝氨酸残基深处开始。因此，催化丝氨酸在外部暴露的空腔中，这为蛋白水解提供了亲水性环境。我们的研究结果揭示了一种机制，使水依赖性的催化在膜的疏水环境的深度，并建议基板如何获得获得的螯合菱形活性位点。
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-angstrom-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.