5DPR

Crystal structure of PLEKHM1 LIR-fused human LC3A_2-121

Summary for 5DPR

• Entry DOI: 10.2210/pdb5dpr/pdb
• Related: 3X0W 5DPS 5DPT 5DPW
• Descriptor: Pleckstrin homology domain-containing family M member 1,Microtubule-associated proteins 1A/1B light chain 3A (2 entities in total)
• Functional Keywords: autophagy; plekhm1; atg8; lc3; gabarap, chimeric protein, protein binding
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 63728.42

Authors

Ravichandran, A.C.,Suzuki, H.,Dobson, R.C.J. (deposition date: 2015-09-14, release date: 2016-09-28, Last modification date: 2024-03-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)