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@ARTICLE{Rogov:120656,
author = {V. V. Rogov and H. Suzuki and M. Marinković and V.
Lang$^*$ and R. Kato and M. Kawasaki and M. Buljubašić and
M. Šprung and N. Rogova and S. Wakatsuki and A.
Hamacher-Brady$^*$ and V. Dötsch and I. Dikic and N.
Brady$^*$ and I. Novak},
title = {{P}hosphorylation of the mitochondrial autophagy receptor
{N}ix enhances its interaction with {LC}3 proteins.},
journal = {Scientific reports},
volume = {7},
number = {1},
issn = {2045-2322},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2017-01083},
pages = {1131},
year = {2017},
abstract = {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.},
cin = {B190},
ddc = {000},
cid = {I:(DE-He78)B190-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28442745},
pmc = {pmc:PMC5430633},
doi = {10.1038/s41598-017-01258-6},
url = {https://inrepo02.dkfz.de/record/120656},
}