The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8
The crystal structure of microtubule-associated protein light chain 3, a mammalian homologue of Saccharomyces cerevisiae Atg8
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DOI：
10.1111/j.1356-9597.2004.00750.x
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发表时间：
2004-07-01
期刊：
影响因子：
2.1
通讯作者：
Inagaki, F
中科院分区：
文献类型：
--
作者：
Sugawara, K;Suzuki, NN;Inagaki, F
微管相关蛋白轻链3（LC 3）是酵母Atg 8的哺乳动物同源物，在自噬中起重要作用，其参与溶酶体系统对细胞质组分的大量降解。在这里，我们报告了LC 3的晶体结构，分辨率为2.05埃，R因子为21.8%，自由R因子为24.9%。LC 3的结构类似于高尔基体相关的ATP酶增强子16 kDa（GATE-16）和GABA（A）受体相关蛋白（GABARAP）的结构，包含一个泛素核心，在其N端连接有两个α螺旋α 1和α 2。在这些蛋白质中观察到一些共同和独特的特征，包括在α 1，α 2和泛素核心之间形成相互作用所需的残基的保守性。然而，这些螺旋的静电势表面不同，暗示特定的角色来选择特定的结合伙伴。LC 3，GABARAP和GATE-16的泛素核心上的疏水补丁是非常保守的，并且与泛素和NEDD 8的E1结合表面相似。因此，我们建议，疏水补丁是哺乳动物Atg 7类似于泛素样缀合系统的结合表面。我们还提出了泛素折叠作为靶蛋白识别模块的功能意义。
Microtubule-associated protein light chain 3 (LC3), a mammalian homologue of yeast Atg8, plays an essential role in autophagy, which is involved in the bulk degradation of cytoplasmic components by the lysosomal system. Here, we report the crystal structure of LC3 at 2.05 Angstrom resolution with an R-factor of 21.8% and a free R-factor of 24.9%. The structure of LC3, which is similar to those of Golgi-associated ATPase enhancer of 16 kDa (GATE-16) and GABA(A) receptor-associated protein (GABARAP), contains a ubiquitin core with two alpha helices, alpha1 and alpha2, attached at its N-terminus. Some common and distinct features are observed among these proteins, including the conservation of residues required to form an interaction among alpha1, alpha2 and the ubiquitin core. However, the electrostatic potential surfaces of these helices differ, implicating particular roles to select specific binding partners. Hydrophobic patches on the ubiquitin core of LC3, GABARAP and GATE-16 are well conserved and are similar to the E1 binding surface of ubiquitin and NEDD8. Therefore, we propose that the hydrophobic patch is a binding surface for mammalian Atg7 similar to a ubiquitin-like conjugation system. We also propose the functional implications of the ubiquitin fold as a recognition module of target proteins.