Dynamic regulation of Zn(II) sequestration by calgranulin C.

Autor: Wang Q; Department of Chemistry, College of Staten Island, City University of New York, New York, New York, USA., Kuci D; Department of Chemistry, College of Staten Island, City University of New York, New York, New York, USA., Bhattacharya S; New York Structural Biology Center, New York, New York, USA., Hadden-Perilla JA; Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware, USA., Gupta R; Department of Chemistry, College of Staten Island, City University of New York, New York, New York, USA.; Ph.D. Programs in Biochemistry and Chemistry, The Graduate Center of the City University of New York, New York, New York, USA.
Jazyk: angličtina
Zdroj: Protein science : a publication of the Protein Society [Protein Sci] 2022 Sep; Vol. 31 (9), pp. e4403.
DOI: 10.1002/pro.4403
Abstrakt: Calgranulin C performs antimicrobial activity in the human immune response by sequestering Zn(II). This biological function is afforded with the aid of two structurally distinct Ca(II)-binding EF hand motifs, wherein one of which bears an unusual amino acid sequence. Here, we utilize solution state NMR relaxation measurements to investigate the mechanism of Ca(II)-modulated enhancement of Zn(II) sequestration by calgranulin C. Using C 13 /N 15 CPMG dispersion experiments we have measured pH-dependent major and minor state populations exchanging on micro-to-millisecond timescale. This conformational exchange takes place exclusively in the Ca(II)-bound state and can be mapped to residues located in the EF-I loop and the linker between the tandem EF hands. Molecular dynamics (MD) simulations spanning nano-to-microsecond timescale offer insights into the role of pH-dependent electrostatic interactions in EF-hand dynamics. Our results suggest a pH-regulated dynamic equilibrium of conformations that explore a range of "closed" and partially "open" sidechain configurations within the Zn(II) binding site. We propose a novel mechanism by which Ca(II) binding to a non-canonical EF loop regulates its flexibility and tunes the antimicrobial activity of calgranulin C.
(© 2022 The Protein Society.)
Databáze: MEDLINE
Externí odkaz: