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@ARTICLE{Lushpa:904336,
author = {Lushpa, Vladislav A. and Goncharuk, Marina V. and Lin, Cong
and Zalevsky, Arthur O. and Talyzina, Irina A. and Luginina,
Aleksandra P. and Vakhrameev, Daniil D. and Shevtsov,
Mikhail B. and Goncharuk, Sergey A. and Arseniev, Alexander
S. and Borshchevskiy, Valentin and Wang, Xiaohui and Mineev,
Konstantin S.},
title = {{M}odulation of {T}oll-like receptor 1 intracellular domain
structure and activity by {Z}n2+ ions},
journal = {Communications biology},
volume = {4},
number = {1},
issn = {2399-3642},
address = {London},
publisher = {Springer Nature},
reportid = {FZJ-2021-05906},
pages = {1003},
year = {2021},
abstract = {Toll-like receptors (TLRs) play an important role in the
innate immune response. While a lot is known about the
structures of their extracellular parts, many questions are
still left unanswered, when the structural basis of TLR
activation is analyzed for the TLR intracellular domains.
Here we report the structure and dynamics of TLR1
toll-interleukin like (TIR) cytoplasmic domain in crystal
and in solution. We found that the TLR1-TIR domain is
capable of specific binding of Zn with nanomolar affinity.
Interactions with Zn are mediated by cysteine residues 667
and 686 and C667 is essential for the Zn binding. Potential
structures of the TLR1-TIR/Zn complex were predicted in
silico. Using the functional assays for the heterodimeric
TLR1/2 receptor, we found that both Zn addition and Zn
depletion affect the activity of TLR1, and C667A mutation
disrupts the receptor activity. Analysis of C667 position in
the TLR1 structure and possible effects of C667A mutation,
suggests that zinc-binding ability of TLR1-TIR domain is
critical for the receptor activation.},
cin = {IBI-7},
ddc = {570},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34429510},
UT = {WOS:000688061400003},
doi = {10.1038/s42003-021-02532-0},
url = {https://juser.fz-juelich.de/record/904336},
}