3X0W

Crystal structure of PLEKHM1 LIR-fused human LC3B_2-119

Summary for 3X0W

• Entry DOI: 10.2210/pdb3x0w/pdb
• Descriptor: Microtubule-associated proteins 1A/1B light chain 3B (2 entities in total)
• Functional Keywords: ubiquitin-like fold, autophagy, plekhm1, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton: Q9GZQ8
• Total number of polymer chains: 2
• Total formula weight: 31463.77

Authors

Suzuki, H.,McEwan, D.G.,Popovic, D.,Gubas, A.,Terawaki, S.,Stadel, D.,Coxon, F.,Stegmann, D.M.,Bhogaraju, S.,Maddi, K.,Kirchhoff, A.,Gatti, E.,Helfrich, M.H.,Behrends, C.,Pierre, P.,Dikic, I.,Wakatsuki, S. (deposition date: 2014-10-22, release date: 2015-01-14, Last modification date: 2023-11-08)

Primary citation

McEwan, D.G.,Popovic, D.,Gubas, A.,Terawaki, S.,Suzuki, H.,Stadel, D.,Coxon, F.P.,Miranda de Stegmann, D.,Bhogaraju, S.,Maddi, K.,Kirchof, A.,Gatti, E.,Helfrich, M.H.,Wakatsuki, S.,Behrends, C.,Pierre, P.,Dikic, I.
PLEKHM1 regulates autophagosome-lysosome fusion through HOPS complex and LC3/GABARAP proteins.
Mol.Cell, 57:39-54, 2015

PubMed Abstract: The lysosome is the final destination for degradation of endocytic cargo, plasma membrane constituents, and intracellular components sequestered by macroautophagy. Fusion of endosomes and autophagosomes with the lysosome depends on the GTPase Rab7 and the homotypic fusion and protein sorting (HOPS) complex, but adaptor proteins that link endocytic and autophagy pathways with lysosomes are poorly characterized. Herein, we show that Pleckstrin homology domain containing protein family member 1 (PLEKHM1) directly interacts with HOPS complex and contains a LC3-interacting region (LIR) that mediates its binding to autophagosomal membranes. Depletion of PLEKHM1 blocks lysosomal degradation of endocytic (EGFR) cargo and enhances presentation of MHC class I molecules. Moreover, genetic loss of PLEKHM1 impedes autophagy flux upon mTOR inhibition and PLEKHM1 regulates clearance of protein aggregates in an autophagy- and LIR-dependent manner. PLEKHM1 is thus a multivalent endocytic adaptor involved in the lysosome fusion events controlling selective and nonselective autophagy pathways.

PubMed: 25498145
DOI: 10.1016/j.molcel.2014.11.006

Experimental method

X-RAY DIFFRACTION (2.71 Å)