Enhanced binding of TBK1 by an optineurin mutant that causes a familial form of primary open angle glaucoma

TANK-binding kinase 1 (TBK1) was identified as a binding partner for Optineurin (OPTN) in two-hybrid screens, an interaction confirmed by overexpression/immunoprecipitation experiments in HEK293 cells and by coimmunoprecipitation of endogenous OPTN and TBK1 from cell extracts. A TBK1 binding site was located between residues 1-127 of OPTN, residues 78-121 displaying striking homology to the TBK1-binding domain of TANK. The OPTN-binding domain was localised to residues 601-729 of TBK1, while TBK1 [1-688] which cannot bind to TANK, did not interact with OPTN. The OPTN[E50K] mutant associated with Primary Open Angle Glaucoma (POAG) displayed strikingly enhanced binding to TBK1, suggesting that this interaction may contribute to familial POAG caused by this mutation. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.