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.
Morton
Simon
S
MRC Protein Phosphorylation Unit, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, UK.
Hesson
Luke
L
Peggie
Mark
M
Cohen
Philip
P
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D018797:Cell Cycle Proteins; D047369:Chromatin Immunoprecipitation; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000378:metabolism; D018698:Glutamic Acid / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000235:genetics; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D035582:Transcription Factor TFIIIA / Q000235:genetics* / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA; D018698:Glutamic Acid; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; D008239:Lysine