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The Ellis van Creveld protein 1 binds and hydrolyzes GTP to a mixture of GMP and GDP and possesses the characteristics of large GTPases
Author(s) -
ODUNUGA ODUTAYO O,
NGUYEN GIANG T
Publication year - 2019
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.2019.33.1_supplement.477.8
Subject(s) - leucine zipper , gtpase , gtp' , g protein , hedgehog , gtp binding protein regulators , smoothened , biology , microbiology and biotechnology , hedgehog signaling pathway , zipper , chemistry , biochemistry , signal transduction , enzyme , peptide sequence , gene , algorithm , computer science
Mutations in the genes that code for EVC1 and EVC2 proteins cause Ellis van Creveld (EvC) syndrome and its milder form, Weyers acrofacial dysostosis (WAD). EVC1 physically binds to EVC2 and together, they are tethered to the base of the primary cilium by the EFCAB7/IQCE protein complex. This multi‐protein assembly positively regulates the Sonic and Indian hedgehog (Hh) signaling pathways by promoting downstream processes after activation of the receptor, smoothened (smo), by the hedgehog proteins. Bioinformatic analysis revealed the presence of several structural motifs in EVC1 sequences including P‐loop, leucine zipper, transmembrane and nuclear localization signal. Using a fragment of EVC1 from mice and humans that contains P‐loop and leucine zipper regions, we present experimental evidence to show that EVC1 protein possesses a high intrinsic GTPase activity with a k cat of ~10 min −1 . In addition, dimerization of EVC1 via its leucine zipper causes the protein to hydrolyze GTP to a mixture of GDP and GMP at unequal ratios. The protein binds GTP at milli to micro molar concentrations, indicating low substrate affinity. These kinetic parameters are similar to those displayed by large GTPases such as Dynamin. We propose that the GTP‐hydrolyzing activity of EVC1 protein is an important mechanistic step in the regulation of the hedgehog signaling pathways. Support or Funding Information Welch Foundation Grant # AN‐0008 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .