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A Comparison of SIKE and WIT 3 Structure and Dynamics
Author(s) -
Machek Megan,
Minzer Ian,
Standen Heather,
Kim SeungHwan,
Latzer Joachim,
Bell Ellis,
Bell Jessica
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1110.1
Subject(s) - chemistry
Suppressor of IKKe (SIKE)inhibits TBK1 mediated phosphorylation of interferon regulatory factor 3 (IRF3) and misregulation of TBK1 is involved in both autoimmune disorders and cancer. Our work (Marion et al, J.Biol.Chem 288, 18612–23, 2013) demonstrated that TBK1 can phosphorylate SIKE in up to 6 positions, altering its ability to inhibit TBK1. Little however is known concerning the three dimensional structure of SIKE. SIKE shares significant homology with WIT3 (known to be involved in wound healing) including several of the phosphorylation sites. It is unknown if these sites cause differences in structure and function. SIKE and WIT3 (both his tagged) have been expressed and SIKE purified using Nickel NTA affinity chromatography and shown to be homogenous by MALDI‐tof mass spectrometry. 3Dimensional models of SIKE and WIT3 and various phosphoforms have been constructed using Phyre2 and subjected to molecular dynamics analysis to further explore structural and dynamic similarities and differences between SIKE and WIT3. In an attempt to validate the models limited proteolysis and Hydrogen Deuterium exchange studies are underway. Support or Funding Information This work was supported by NIH grant R21A1 107447 to JKB