4waa | pdb_00004waa

Crystal structure of Nix LIR-fused human LC3B_2-119

spinqualitylabelsall models 4waa, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4waa is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.35Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MLP3B_HUMAN Involved in formation of autophagosomal vacuoles (autophagosomes). Publication Abstract from PubMed The mitophagy receptor Nix interacts with LC3/GABARAP proteins, targeting mitochondria into autophagosomes for degradation. Here we present evidence for phosphorylation-driven regulation of the Nix:LC3B interaction. Isothermal titration calorimetry and NMR indicate a ~100 fold enhanced affinity of the serine 34/35-phosphorylated Nix LC3-interacting region (LIR) to LC3B and formation of a very rigid complex compared to the non-phosphorylated sequence. Moreover, the crystal structure of LC3B in complex with the Nix LIR peptide containing glutamic acids as phosphomimetic residues and NMR experiments revealed that LIR phosphorylation stabilizes the Nix:LC3B complex via formation of two additional hydrogen bonds between phosphorylated serines of Nix LIR and Arg11, Lys49 and Lys51 in LC3B. Substitution of Lys51 to Ala in LC3B abrogates binding of a phosphomimetic Nix mutant. Functionally, serine 34/35 phosphorylation enhances autophagosome recruitment to mitochondria in HeLa cells. Together, this study provides cellular, biochemical and biophysical evidence that phosphorylation of the LIR domain of Nix enhances mitophagy receptor engagement. Phosphorylation of the mitochondrial autophagy receptor Nix enhances its interaction with LC3 proteins.,Rogov VV, Suzuki H, Marinkovic M, Lang V, Kato R, Kawasaki M, Buljubasic M, Sprung M, Rogova N, Wakatsuki S, Hamacher-Brady A, Dotsch V, Dikic I, Brady NR, Novak I Sci Rep. 2017 Apr 25;7(1):1131. doi: 10.1038/s41598-017-01258-6. PMID:28442745 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Microtubule-associated protein 3D structures

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