Modulation of Toll-like receptor 1 intracellular domain structure and activity by Zn(2+) ions.
Modulation of Toll-like receptor 1 intracellular domain structure and activity by Zn(2+) ions.
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Zn2 离子对 Toll 样受体 1 胞内结构域结构和活性的调节
DOI：
10.1038/s42003-021-02532-0
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发表时间：
2021-08-24
影响因子：
5.9
通讯作者：
Mineev KS
中科院分区：
文献类型：
--
作者：
Lushpa VA;Goncharuk MV;Lin C;Zalevsky AO;Talyzina IA;Luginina AP;Vakhrameev DD;Shevtsov MB;Goncharuk SA;Arseniev AS;Borshchevskiy VI;Wang X;Mineev KS
Toll 样受体 (TLR) 在先天免疫反应中发挥着重要作用。虽然人们对其细胞外部分的结构了解很多，但在分析 TLR 细胞内结构域的 TLR 激活的结构基础时，许多问题仍未得到解答。在这里，我们报告了晶体和溶液中 TLR1 Toll 白细胞介素样 (TIR) 胞质结构域的结构和动力学。我们发现 TLR1-TIR 结构域能够以纳摩尔亲和力特异性结合 Zn。与 Zn 的相互作用由半胱氨酸残基 667 和 686 介导，C667 对于 Zn 结合至关重要。通过计算机预测了 TLR1-TIR/Zn 复合物的潜在结构。通过对异二聚体 TLR1/2 受体的功能测定，我们发现 Zn 添加和 Zn 消耗都会影响 TLR1 的活性，并且 C667A 突变会破坏受体活性。对 TLR1 结构中 C667 位置和 C667A 突变的可能影响的分析表明，TLR1-TIR 结构域的锌结合能力对于受体激活至关重要。 Lushpa 等人报道了晶体和溶液中 TLR1 toll 白细胞介素样 (TIR) 胞质结构域的结构和动力学。他们证明，TLR1 TIR 结构域能够以纳摩尔亲和力特异性结合 Zn，这似乎对于受体激活至关重要，并基于计算机数据提供了 TLR1-TIR/Zn 复合物的潜在结构。
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. Lushpa et al report the structure and dynamics of the TLR1 toll-interleukin like (TIR) cytoplasmic domain in both crystal and solution. They demonstrate that the TLR1 TIR domain is capable of specific binding of Zn with nanomolar affinity, which appears to be critical for receptor activation, and provide potential structures TLR1-TIR/Zn complex based on in silico data.
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影响因子：
2.7
作者：
Chill, Jordan H.;Louis, John M.;Bax, Ad
通讯作者：
Bax, Ad
影响因子：
1.6
作者：
Goncharuk, Marina V.;Lushpa, Vladislav A.;Mineev, Konstantin S.
通讯作者：
Mineev, Konstantin S.
影响因子：
4.4
作者：
Haase, Hajo;Ober-Bloebaum, Julia L.;Rink, Lothar
通讯作者：
Rink, Lothar
DOI：
10.1073/pnas.0505077102
发表时间：
2005-08-02
影响因子：
11.1
作者：
Bell, JK;Botos, I;Davies, DR
通讯作者：
Davies, DR
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH