Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
EMBO Rep. 2014 May;15(5):557-65. doi: 10.1002/embr.201338003. Epub 2014 Mar 25.
Several autophagy proteins contain an LC3-interacting region (LIR) responsible for their interaction with Atg8 homolog proteins. Here, we show that ALFY binds selectively to LC3C and the GABARAPs through a LIR in its WD40 domain. Binding of ALFY to GABARAP is indispensable for its recruitment to LC3B-positive structures and, thus, for the clearance of certain p62 structures by autophagy. In addition, the crystal structure of the GABARAP-ALFY-LIR peptide complex identifies three conserved residues in the GABARAPs that are responsible for binding to ALFY. Interestingly, introduction of these residues in LC3B is sufficient to enable its interaction with ALFY, indicating that residues outside the LIR-binding hydrophobic pockets confer specificity to the interactions with Atg8 homolog proteins.
几种自噬蛋白含有一个 LC3 相互作用区域（LIR），负责与 Atg8 同源蛋白相互作用。在这里，我们表明，ALFY 通过其 WD40 结构域中的 LIR 选择性地结合 LC3C 和 GABARAPs。ALFY 与 GABARAP 的结合对于其募集到 LC3B 阳性结构以及通过自噬清除某些 p62 结构是必不可少的。此外，GABARAP-ALFY-LIR 肽复合物的晶体结构确定了 GABARAPs 中三个保守残基，这些残基负责与 ALFY 结合。有趣的是，在 LC3B 中引入这些残基足以使其与 ALFY 相互作用，表明 LIR 结合疏水性口袋之外的残基赋予与 Atg8 同源蛋白相互作用的特异性。
