Bosch Jürgen, Tamura Tomohiro, Tamura Noriko, Baumeister Wolfgang, Essen Lars-Oliver
Max-Planck-Institute for Biochemistry, Department of Molecular Structural Biology, Am Klopferspitz 18a, D-82152 Martinsried, Germany.
Acta Crystallogr D Biol Crystallogr. 2007 Feb;63(Pt 2):179-87. doi: 10.1107/S0907444906045471. Epub 2007 Jan 16.
In the proteolytic pathway of prokaryotic and eukaryotic organisms, proteins tagged for proteolysis are firstly shredded into smaller peptides by compartmentalized proteases such as the proteasome complex. Accordingly, a variety of downstream proteases have evolved to further hydrolyze these peptides to the level of free amino acids. In the search for such downstream proteases, a high-molecular-weight protease complex called trilobed protease (TLP) was recently discovered in the archaeon Pyroccocus furiosus. The crystal structure of the N-terminal beta-propeller domain of the trilobed protease at 2 A resolution shows that the trilobed protease utilizes this accessory domain to control substrate access to the active site. Modelling of the intact TLP monomer suggests that this protease has an additional side entrance to its active site as in the DPP-IV or tricorn protease complexes.
在原核生物和真核生物的蛋白水解途径中，被标记用于蛋白水解的蛋白质首先被诸如蛋白酶体复合物等区室化蛋白酶切割成较小的肽段。相应地，多种下游蛋白酶已经进化出来，以进一步将这些肽水解为游离氨基酸水平。在寻找此类下游蛋白酶的过程中，最近在古菌激烈火球菌中发现了一种称为三叶蛋白酶（TLP）的高分子量蛋白酶复合物。三叶蛋白酶N端β-螺旋桨结构域在2埃分辨率下的晶体结构表明，三叶蛋白酶利用这个辅助结构域来控制底物进入活性位点。完整TLP单体的建模表明，这种蛋白酶像二肽基肽酶IV或三触角蛋白酶复合物一样，其活性位点还有一个额外的侧面入口。
