Open AccessMechanism of Zinc Transport through the Zinc Transporter YiiP
Author(s) -
Gaurav Sharma,
Kenneth M. Merz
Publication year - 2022
Publication title -
journal of chemical theory and computation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.001
H-Index - 185
eISSN - 1549-9626
pISSN - 1549-9618
DOI - 10.1021/acs.jctc.1c00927
Subject(s) - zinc , transporter , efflux , molecular dynamics , chemistry , transmembrane protein , lipid bilayer , biophysics , mechanism (biology) , ion transporter , function (biology) , membrane , biochemistry , biology , microbiology and biotechnology , computational chemistry , physics , gene , receptor , organic chemistry , quantum mechanics
Zinc is an essential transition metal ion that plays as a structural, functional (catalytic), and a signaling molecule regulating cellular function. Unbalanced levels of zinc in cells can result in various pathological conditions. In the current work, all-atom molecular dynamics simulations were used to study the structure-function correlation between different YiiP states embedded in a lipid bilayer. This study enabled us to develop a hypothesis on the zinc efflux mechanism of YiiP. We have created six different models of YiiP representing the stages of the ion-transport process. We found that zinc ion plays a crucial role in restraining the transmembrane domains (TMDs) of the protein. In addition, H153, located in the TMD, has been proposed to guide the zinc ion toward the ZnA site of the YiiP transporter. Understanding the molecular-level Zn 2+ -transport process sheds light on the strategies affecting intracellular transition-metal ion concentrations in order to treat diseases like diabetes and cancer.