8C2D

14-3-3 in complex with Pyrin pS208

This is a non-PDB format compatible entry.

Summary for 8C2D

• Entry DOI: 10.2210/pdb8c2d/pdb
• Descriptor: 14-3-3 protein sigma, Pyrin pS208 peptide, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: protein-peptide interaction, phosphorylation reader protein, immunology, scaffolding, intrinsic disorder motif, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 28651.28

Authors

Lau, R.,Ottmann, C.,Hann, M. (deposition date: 2022-12-22, release date: 2023-07-26, Last modification date: 2024-11-13)

Primary citation

Lau, R.,Hann, M.M.,Ottmann, C.
Crystal structure and ligandability of the 14-3-3/pyrin interface.
Biochem.Biophys.Res.Commun., 651:1-7, 2023

PubMed Abstract: Overactivation of Pyrin is the cause of the inflammatory diseases Mediterranean Fever and Pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). Binding of 14-3-3 proteins reduces the pro-inflammatory activity of Pyrin, hence small molecules that stabilize the Pyrin/14-3-3 complex could convey an anti-inflammatory effect. We have solved the atomic resolution crystal structures of phosphorylated peptides derived from PyrinpS208 and PyrinpS242 - the two principle 14-3-3 binding sites in Pyrin - in complex with 14-3-3 and analyzed the ligandability of these protein-peptide interfaces by crystal-based fragment soaking. The complex between 14-3-3 and PyrinpS242 appears to be much more amenable for small-molecule binding than that of 14-3-3/PyrinpS208. Consequently, only for the 14-3-3/PyrinpS242 complex could we find an interface-binding fragment, validating protein crystallography and fragment soaking as a method to evaluate the ligandability of protein surfaces.

PubMed: 36774661
DOI: 10.1016/j.bbrc.2023.02.013

Experimental method

X-RAY DIFFRACTION (2.15 Å)