A combined biochemical and cellular approach reveals Zn <superscript>2+</superscript> -dependent hetero- and homodimeric CD4 and Lck assemblies in T cells.
In: Structure (London, England : 1993), Jg. 32 (2024-03-07), Heft 3, S. 292-303.e7
academicJournal
Zugriff:
The CD4 or CD8 co-receptors' interaction with the protein-tyrosine kinase Lck initiates the tyrosine phosphorylation cascade leading to T cell activation. A critical question is: to what extent are co-receptors and Lck coupled? Our contribution concerns Zn 2+ , indispensable for CD4 - and CD8-Lck formation. We combined biochemical and cellular approaches to show that dynamic fluctuations of free Zn 2+ in physiological ranges influence Zn(CD4) 2 and Zn(CD4)(Lck) species formation and their ratio, although the same Zn(Cys) 2 (Cys) 2 cores. Moreover, we demonstrated that the affinity of Zn 2+ to CD4 and CD4-Lck species differs significantly. Increased intracellular free Zn 2+ concentration in T cells causes higher CD4 partitioning in the plasma membrane. We additionally found that CD4 palmitoylation decreases the specificity of CD4-Lck formation in the reconstituted membrane model. Our findings help elucidate co-receptor-Lck coupling stoichiometry and demonstrate that intracellular free Zn 2+ has a major role in the interplay between CD4 dimers and CD4-Lck assembly.
Competing Interests: Declaration of interests There is no competing interest to declare.
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Titel: |
A combined biochemical and cellular approach reveals Zn <superscript>2+</superscript> -dependent hetero- and homodimeric CD4 and Lck assemblies in T cells.
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Autor/in / Beteiligte Person: | Kocyła, AM ; Czogalla, A ; Wessels, I ; Rink, L ; Krężel, A |
Zeitschrift: | Structure (London, England : 1993), Jg. 32 (2024-03-07), Heft 3, S. 292-303.e7 |
Veröffentlichung: | 2000- : Cambridge, Mass. : Cell Press ; <i>Original Publication</i>: London : Current Biology, c1993-, 2024 |
Medientyp: | academicJournal |
ISSN: | 1878-4186 (electronic) |
DOI: | 10.1016/j.str.2023.11.013 |
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