Zinc-mediated dynamics of CD4/CD8α co-receptors and Lck kinase: implications for zinc homeostasis, immune response, and biotechnological innovations.

Abstract

Zinc (Zn²⁺) plays a pivotal role in T-cell activation by modulating the interactions between the co-receptors CD4 and CD8α and the Src-family kinase Lck. A central structural feature in this regulation is the zinc clasp, a Zn²⁺-mediated CD4/CD8α-Lck receptor interface that stabilizes these complexes during T cell receptor signaling. Recent findings reveal that the stability of CD4-Lck and CD8α-Lck complexes is differentially regulated by Zn²⁺, which acts as a dynamic signaling molecule during T-cell activation. Here, we discuss the structural dynamics of these interactions and the impact of Zn²⁺ on CD4 dimerization, palmitoylation, and membrane interactions, which are crucial for effective T-cell responses. These mechanisms underscore a broader framework in which zinc biology intersects with co-receptor-Lck coupling to guide T-cell development, lineage fidelity, and functional specialization. Beyond immunobiology, zinc-dependent protein-protein interactions offer promising opportunities for biotechnological innovation, particularly in the design of molecular systems that exploit zinc-mediated structural control.