与FYCO1的LC3相互作用区域（LIR）结合的小鼠微管相关蛋白1轻链3β（LC3B）的晶体结构揭示了LIR基序侧翼区域的重要性。
The crystal structure of mouse LC3B in complex with the FYCO1 LIR reveals the importance of the flanking region of the LIR motif.
作者信息
Sakurai Shunya, Tomita Taisuke, Shimizu Toshiyuki, Ohto Umeharu
机构信息
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
出版信息
Acta Crystallogr F Struct Biol Commun. 2017 Mar 1;73(Pt 3):130-137. doi: 10.1107/S2053230X17001911. Epub 2017 Feb 21.
Abstract
FYVE and coiled-coil domain-containing protein 1 (FYCO1), a multidomain autophagy adaptor protein, mediates microtubule plus-end-directed autophagosome transport by interacting with kinesin motor proteins and with the autophagosomal membrane components microtubule-associated protein 1 light chain 3 (LC3), Rab7 and phosphatidylinositol 3-phosphate (PI3P). To establish the structural basis for the recognition of FYCO1 by LC3, the crystal structure of mouse LC3B in complex with the FYCO1 LC3-interacting region (LIR) motif peptide was determined. Structural analysis showed that the flanking sequences N-terminal and C-terminal to the LIR core sequence of FYCO1, as well as the tetrapeptide core sequence, were specifically recognized by LC3B and contributed to the binding. Moreover, comparisons of related structures revealed a conserved mechanism of FYCO1 recognition by different LC3 isoforms among different species.
摘要
含FYVE和卷曲螺旋结构域蛋白1（FYCO1）是一种多结构域自噬衔接蛋白，通过与驱动蛋白运动蛋白以及自噬体膜成分微管相关蛋白1轻链3（LC3）、Rab7和磷脂酰肌醇3-磷酸（PI3P）相互作用，介导微管正端定向的自噬体转运。为了确定LC3识别FYCO1的结构基础，我们测定了与FYCO1的LC3相互作用区域（LIR）基序肽形成复合物的小鼠LC3B的晶体结构。结构分析表明，FYCO1的LIR核心序列N端和C端的侧翼序列以及四肽核心序列被LC3B特异性识别并有助于结合。此外，相关结构的比较揭示了不同物种中不同LC3亚型识别FYCO1的保守机制。
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