5D94

Crystal structure of LC3-LIR peptide complex

5D94 の概要

• エントリーDOI: 10.2210/pdb5d94/pdb
• 分子名称: Microtubule-associated proteins 1A/1B light chain 3B, Peptide from FYVE and coiled-coil domain-containing protein 1 (3 entities in total)
• 機能のキーワード: fyco1, autophagy, lc3, lir, protein binding-peptide complex, protein binding/peptide
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 16616.04

構造登録者

Takagi, K.,Mizushima, T.,Johansen, T. (登録日: 2015-08-18, 公開日: 2015-10-21, 最終更新日: 2024-03-20)

主引用文献

Olsvik, H.L.,Lamark, T.,Takagi, K.,Larsen, K.B.,Evjen, G.,vervatn, A.,Mizushima, T.,Johansen, T.
FYCO1 Contains a C-terminally Extended, LC3A/B-preferring LC3-interacting Region (LIR) Motif Required for Efficient Maturation of Autophagosomes during Basal Autophagy
J.Biol.Chem., 290:29361-29374, 2015

PubMed Abstract: FYCO1 (FYVE and coiled-coil protein 1) is a transport adaptor that binds to phosphatidylinositol 3-phosphate, to Rab7, and to LC3 (microtubule-associated protein 1 light chain 3) to mediate transport of late endosomes and autophagosomes along microtubules in the plus end direction. We have previously shown that FYCO1 binds to LC3B via a 19-amino acid sequence containing a putative core LC3-interacting region (LIR) motif. Here, we show that FYCO1 preferentially binds to LC3A and -B. By peptide array-based two-dimensional mutational scans of the binding to LC3B, we found FYCO1 to contain a C-terminally extended LIR domain. We determined the crystal structure of a complex between a 13-amino acid LIR peptide from FYCO1 and LC3B at 1.53 Å resolution. By combining the structural information with mutational analyses, both the basis for the C-terminally extended LIR and the specificity for LC3A/B binding were revealed. FYCO1 contains a 9-amino acid-long F-type LIR motif. In addition to the canonical aromatic residue at position 1 and the hydrophobic residue at position 3, an acidic residue and a hydrophobic residue at positions 8 and 9, respectively, are important for efficient binding to LC3B explaining the C-terminal extension. The specificity for binding to LC3A/B is due to the interaction between Asp(1285) in FYCO1 and His(57) in LC3B. To address the functional significance of the LIR motif of FYCO1, we generated FYCO1 knock-out cells that subsequently were reconstituted with GFP-FYCO1 WT and LIR mutant constructs. Our data show that FYCO1 requires a functional LIR motif to facilitate efficient maturation of autophagosomes under basal conditions, whereas starvation-induced autophagy was unaffected.

PubMed: 26468287
DOI: 10.1074/jbc.M115.686915

実験手法

X-RAY DIFFRACTION (1.53 Å)