Calcium Regulates S100A12 Zinc Sequestration by Limiting Structural Variations.
Calcium Regulates S100A12 Zinc Sequestration by Limiting Structural Variations.
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钙通过限制结构变化来调节 S100A12 锌的螯合。
DOI：
10.1002/cbic.201900623
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Gupta,Rupal
中科院分区：
文献类型：
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作者：
Wang,Qian;Aleshintsev,Aleksey;Jose,AneeshaN;Aramini,JamesM;Gupta,Rupal
Antimicrobial proteins such as S100A12 and S100A8/A9 are highly expressed and secreted by neutrophils during infection and participate in human immune response by sequestering transition metals. At neutral pH, S100A12 sequesters Zn2+with nanomolar affinity, which is further enhanced upon calcium binding. We investigated the pH dependence of human S100A12 zinc sequestration by using Co2+as a surrogate. Apo‐S100A12 exhibits strong Co2+binding between pH 7.0 and 10.0 that progressively diminishes as the pH is decreased to 5.3. Ca2+‐S100A12 can retain nanomolar Co2+binding up to pH 5.7. NMR spectroscopic measurements revealed that calcium binding does not alter the side‐chain protonation of the Co2+/Zn2+binding histidine residues. Instead, the calcium‐mediated modulation is achieved by restraining pH‐dependent conformational changes to EF loop 1, which contains Co2+/Zn2+binding Asp25. This calcium‐induced enhancement of Co2+/Zn2+binding might assist in the promotion of antimicrobial activities in humans by S100 proteins during neutrophil activation under subneutral pH conditions.
