Morton Simon, Hesson Luke, Peggie Mark, Cohen Philip
MRC Protein Phosphorylation Unit, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, UK.
FEBS Lett. 2008 Mar 19;582(6):997-1002. doi: 10.1016/j.febslet.2008.02.047. Epub 2008 Feb 26.
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.
在双杂交筛选中， Tank结合激酶1（TBK1）被鉴定为视紫质（OPTN）的结合伙伴，HEK293细胞中的过表达/免疫沉淀实验以及从细胞提取物中内源性OPTN和TBK1的共免疫沉淀证实了这种相互作用。TBK1结合位点位于OPTN的1-127位残基之间，78-121位残基与TANK的TBK1结合域具有显著同源性。OPTN结合域定位于TBK1的601-729位残基，而不能与TANK结合的TBK1[1-688]不与OPTN相互作用。与原发性开角型青光眼（POAG）相关的OPTN[E50K]突变体与TBK1的结合显著增强，表明这种相互作用可能导致该突变引起的家族性POAG。
