Work

Calcium Regulates S100A12 Zinc Sequestration by Limiting Structural Variations

Year: 2019

Type: article

Abstract: 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.

Source: ChemBioChem

DOI: 10.1002/cbic.201900623

Authors: Qian Wang, Aleksey Aleshintsev, Aneesha N. Jose, James M. Aramini, Rupal Gupta

Institutions: College of Staten Island, City University of New York, The Graduate Center, CUNY, CUNY Advanced Science Research Center

Language: English

Topic: S100 Proteins and Annexins

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, Research Foundation of The City University of New York, National Institute of General Medical Sciences