5DPT

Crystal structure of PLEKHM1 LIR-fused human GABARAPL1_2-117

5DPT の概要

• エントリーDOI: 10.2210/pdb5dpt/pdb
• 関連するPDBエントリー: 3X0W 5DPR 5DPS 5DPW
• 分子名称: Pleckstrin homology domain-containing family M member 1, Gamma-aminobutyric acid receptor-associated protein-like 1,Gamma-aminobutyric acid receptor-associated protein-like 1, (4S)-2-METHYL-2,4-PENTANEDIOL (2 entities in total)
• 機能のキーワード: autophagy, chimeric protein, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31649.80

構造登録者

Ravichandran, A.C.,Suzuki, H.,Dobson, R.C.J. (登録日: 2015-09-14, 公開日: 2016-09-28, 最終更新日: 2024-03-06)

主引用文献

Rogov, V.V.,Stolz, A.,Ravichandran, A.C.,Rios-Szwed, D.O.,Suzuki, H.,Kniss, A.,Lohr, F.,Wakatsuki, S.,Dotsch, V.,Dikic, I.,Dobson, R.C.,McEwan, D.G.
Structural and functional analysis of the GABARAP interaction motif (GIM).
EMBO Rep., 18:1382-1396, 2017

PubMed Abstract: Through the canonical LC3 interaction motif (LIR), [W/F/Y]-X-X-[I/L/V], protein complexes are recruited to autophagosomes to perform their functions as either autophagy adaptors or receptors. How these adaptors/receptors selectively interact with either LC3 or GABARAP families remains unclear. Herein, we determine the range of selectivity of 30 known core LIR motifs towards individual LC3s and GABARAPs. From these, we define a ABARAP nteraction otif (GIM) sequence ([W/F]-[V/I]-X-V) that the adaptor protein PLEKHM1 tightly conforms to. Using biophysical and structural approaches, we show that the PLEKHM1-LIR is indeed 11-fold more specific for GABARAP than LC3B. Selective mutation of the X and X positions either completely abolished the interaction with all LC3 and GABARAPs or increased PLEKHM1-GIM selectivity 20-fold towards LC3B. Finally, we show that conversion of p62/SQSTM1, FUNDC1 and FIP200 LIRs into our newly defined GIM, by introducing two valine residues, enhances their interaction with endogenous GABARAP over LC3B. The identification of a GABARAP-specific interaction motif will aid the identification and characterization of the expanding array of autophagy receptor and adaptor proteins and their functions.

PubMed: 28655748
DOI: 10.15252/embr.201643587

実験手法

X-RAY DIFFRACTION (2.9 Å)