Liao Jiahn-Haur, Ihara Kentaro, Kuo Chiao-I, Huang Kai-Fa, Wakatsuki Soichi, Wu Shih-Hsiung, Chang Chung-I
Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan.
Acta Crystallogr D Biol Crystallogr. 2013 Aug;69(Pt 8):1395-402. doi: 10.1107/S0907444913008214. Epub 2013 Jul 13.
The Lon proteases are a unique family of chambered proteases with a built-in AAA+ (ATPases associated with diverse cellular activities) module. Here, crystal structures of a unique member of the Lon family with no intrinsic ATPase activity in the proteolytically active form are reported both alone and in complexes with three covalent inhibitors: two peptidomimetics and one derived from a natural product. This work reveals the unique architectural features of an ATP-independent Lon that selectively degrades unfolded protein substrates. Importantly, these results provide mechanistic insights into the recognition of inhibitors and polypeptide substrates within the conserved proteolytic chamber, which may aid the development of specific Lon-protease inhibitors.
Lon蛋白酶是一类独特的有腔室蛋白酶家族，带有一个内置的AAA+（与多种细胞活动相关的ATP酶）模块。本文报道了Lon家族中一个独特成员的晶体结构，该成员在蛋白水解活性形式下没有内在ATP酶活性，其单独结构以及与三种共价抑制剂（两种拟肽和一种天然产物衍生物）形成的复合物的结构。这项工作揭示了一种不依赖ATP的Lon的独特结构特征，该Lon能选择性地降解未折叠的蛋白质底物。重要的是，这些结果为保守蛋白水解腔室内抑制剂和多肽底物的识别提供了机制性见解，这可能有助于开发特异性Lon蛋白酶抑制剂。
