Recent advances in factor XII structure and function
Current opinion in hematology, 2022•journals.lww.com
We propose a model in which FXII is normally maintained in a closed conformation resistant
to activation by intramolecular interactions involving the fibronectin type-2 and kringle
domains. These interactions are disrupted when FXII binds to a surface through EGF1,
enhancing FXII activation and prekallikrein activation by FXIIa. These observations have
important implications for understanding the contributions of FXII to disease, and for
developing therapies to treat thrombo-inflammatory disorders.
to activation by intramolecular interactions involving the fibronectin type-2 and kringle
domains. These interactions are disrupted when FXII binds to a surface through EGF1,
enhancing FXII activation and prekallikrein activation by FXIIa. These observations have
important implications for understanding the contributions of FXII to disease, and for
developing therapies to treat thrombo-inflammatory disorders.
Summary
We propose a model in which FXII is normally maintained in a closed conformation resistant to activation by intramolecular interactions involving the fibronectin type-2 and kringle domains. These interactions are disrupted when FXII binds to a surface through EGF1, enhancing FXII activation and prekallikrein activation by FXIIa. These observations have important implications for understanding the contributions of FXII to disease, and for developing therapies to treat thrombo-inflammatory disorders.
Lippincott Williams & Wilkins