A cryptic symmetry switch allosterically controls how the PF4 self-protein turns into a pathogenic antigen.

Abstract excerpt

The asymmetry of dimers-of-dimers formed by Platelet Factor 4 (PF4) renders this endogenous protein immunogenic, triggering autoimmune responses such as heparin-induced thrombocytopenia (HIT). Yet, the molecular basis of PF4 asymmetry has remained elusive. Here, we show that cryptic conformational switches control PF4 tetramer asymmetry and explain how a benign self-protein morphs into an immunogenic antigen,...

Topics

• Platelet Factor 4
• Humans
• Autoantigens
• Protein Multimerization
• Allosteric Regulation
• Heparin