Mechanism of Zn²⁺ and Ca²⁺ Binding to Human S100A1.

ABSTRACT: S100A1 is a member of the S100 family of small ubiquitous Ca²⁺-binding proteins, which participates in the regulation of cell differentiation, motility, and survival. It exists as homo- or heterodimers. S100A1 has also been shown to bind Zn²⁺, but the molecular mechanisms of this binding are not yet known. In this work, using ESI-MS and ITC, we demonstrate that S100A1 can coordinate 4 zinc ions per monomer, with two high affinity (K_D~4 and 770 nm) and two low affinity sites. Using competitive binding experiments between Ca²⁺ and Zn²⁺ and QM/MM molecular modeling we conclude that Zn²⁺ high affinity sites are located in the EF-hand motifs of S100A1. In addition, two lower affinity sites can bind Zn²⁺ even when the E

SUBMITTER: Baksheeva VE 

PROVIDER: S-EPMC8699212 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature