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Calcium Regulates S100A12 Zinc Sequestration by Limiting Structural Variations
Author(s) -
Wang Qian,
Aleshintsev Aleksey,
Jose Aneesha N.,
Aramini James M.,
Gupta Rupal
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900623
Subject(s) - chemistry , calcium , histidine , zinc , biophysics , protonation , biochemistry , plasma protein binding , enzyme , biology , organic chemistry , ion
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 Zn 2+ with nanomolar affinity, which is further enhanced upon calcium binding. We investigated the pH dependence of human S100A12 zinc sequestration by using Co 2+ as a surrogate. Apo‐S100A12 exhibits strong Co 2+ binding between pH 7.0 and 10.0 that progressively diminishes as the pH is decreased to 5.3. Ca 2+ ‐S100A12 can retain nanomolar Co 2+ binding up to pH 5.7. NMR spectroscopic measurements revealed that calcium binding does not alter the side‐chain protonation of the Co 2+ /Zn 2+ binding histidine residues. Instead, the calcium‐mediated modulation is achieved by restraining pH‐dependent conformational changes to EF loop 1, which contains Co 2+ /Zn 2+ binding Asp25. This calcium‐induced enhancement of Co 2+ /Zn 2+ binding might assist in the promotion of antimicrobial activities in humans by S100 proteins during neutrophil activation under subneutral pH conditions.