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The first crystal structure of cyclic GMP‐dependent protein kinase Iβ dimerization domain reveals the molecular features of an extended leucine/isoleucine zipper
Author(s) -
Kim Choel,
SmithNguyen Eric V.,
Casteel Darren E.,
Sankaran Banumathi,
Spraggon Glen,
Pilz Renate B.,
Taylor Susan S.
Publication year - 2008
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.22.1_supplement.828.4
Subject(s) - leucine zipper , chemistry , docking (animal) , crystallography , protein structure , static electricity , stereochemistry , biophysics , peptide sequence , biochemistry , biology , physics , medicine , quantum mechanics , gene , nursing
Subcellular targeting of cyclic GMP‐dependent protein kinase (PKG) provides an important mechanism for achieving substrate specificity and is mediated by the N‐terminal dimerization (ND) domain, which binds to defined sets of protein substrates in an isotype dependent manner. Although ND of PKG Iβ has previously been shown to provide a unique docking surface for TFII‐I and IRAG, the structural detail of this protein‐protein recognition surface was unknown. In order to understand the subcellular targeting mechanism of PKG Iβ and the molecular detail of the protein docking motif, we solved a crystal structure of the ND of PKG Iβ at 2.1 angstrom. The structure reveals two N‐terminal helices warping around each other into a left‐handed helix and forming an extended leu/ile zipper with 10 pairs of leu/ile packing in a “knobs‐into‐holes” manner. The interaction interface consists of negatively charged residues surrounding a pronounced hydrophobic patch. Surprisingly, the structure also reveals two positively charged residues at the d positions (rather than at the canonical g positions) forming interhelical electrostatic interactions with two negatively charged residues at the e positions in a mirror symmetry fashion. The electrostatic pairs flanking the interaction interface may aid in stabilizing the docking surface crucial for specifically binding IRAG and TFII‐I.