6ZCJ

14-3-3sigma in complex with SLP76pS376 phosphopeptide crystal structure

Summary for 6ZCJ

• Entry DOI: 10.2210/pdb6zcj/pdb
• Descriptor: 14-3-3 protein sigma, SLP76pS376, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: adaptor protein, phosphorylation, peptide binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 27850.65

Authors

Soini, L.,Leysen, S.,Davis, J.,Ottmann, C. (deposition date: 2020-06-11, release date: 2020-12-02, Last modification date: 2024-11-20)

Primary citation

Soini, L.,Leysen, S.,Davis, J.,Westwood, M.,Ottmann, C.
The 14-3-3/SLP76 protein-protein interaction in T-cell receptor signalling: a structural and biophysical characterization.
Febs Lett., 595:404-414, 2021

PubMed Abstract: The SH2 domain-containing protein of 76 kDa, SLP76, is an important adaptor protein that coordinates a complex protein network downstream of T-cell receptors (TCR), ultimately regulating the immune response. Upon phosphorylation on Ser376, SLP76 interacts with 14-3-3 adaptor proteins, which leads to its proteolytic degradation. This provides a negative feedback mechanism by which TCR signalling can be controlled. To gain insight into the 14-3-3/SLP76 protein-protein interaction (PPI), we have determined a high-resolution crystal structure of a SLP76 synthetic peptide containing Ser376 with 14-3-3σ. We then characterized its binding to 14-3-3 proteins biophysically by means of fluorescence polarization and isothermal titration calorimetry. Furthermore, we generated two recombinant SLP76 protein constructs and characterized their binding to 14-3-3. Our work lays the foundation for drug design efforts aimed at targeting the 14-3-3/SLP76 interaction and, thereby, TCR signalling.

PubMed: 33159816
DOI: 10.1002/1873-3468.13993

Experimental method

X-RAY DIFFRACTION (1.53 Å)