A Trap-Door Mechanism for Zinc Acquisition by <i>Streptococcus pneumoniae</i> AdcA
Zhenyao Luo, Jacqueline R. Morey, Evelyne Deplazes, Alina Motygullina, Aimee Tan, Katherine Ganio, Stephanie L. Neville, Nikolaos Eleftheriadis, Michael Isselstein, Victoria G. Pederick, James C. Paton, Thorben Cordes, Jeffrey R. Harmer, Boštjan Kobe, Christopher A. McDevitt
Abstract
, and use computational, spectroscopic, and microbiological approaches to provide new insights into the functional basis of zinc recruitment. Our findings reveal that AdcA employs a novel mechanism for zinc binding that we have termed the "trap-door" mechanism, and we show how the static metal-binding site of the protein, which confers its selectivity for zinc ions, is combined with a dynamic surface element to facilitate zinc recruitment and import into the bacterium. Together, these findings expand our understanding of how bacteria acquire zinc from the environment and provide a foundation for inhibiting this process, through antimicrobial targeting of the dynamic structural elements to block bacterial zinc scavenging.