The crystal structure of the NTF2-like domain of the human Ras GTPase SH3
Binding Protein (G3BP), isoform 2, was determined at a resolution of 2.75 Å in
complex with a peptide containing a FGDF sequence motif. The overall structure
of the protein is highly similar to the homodimeric N-terminal domains of the
G3BP1 and Rasputin proteins. Recently, a subset of G3BP interacting proteins was
recognized to share a common sequence motif, FGDF. The most studied binding
partners, USP10 and viral nsP3, interfere with essential G3BP functions related
to assembly of cellular stress granules. Reported molecular modeling suggested
that FGDF-motif containing peptides bind in an extended conformation into a
hydrophobic groove on the surface of the G3BP NTF2-like domain in a manner
similar to the known binding of FxFG nucleoporin repeats. The results in this
paper provide evidence for a different binding mode. The FGDF peptide binds and
changes conformation of the protruding N-terminal residues by providing
hydrophobic interactions to a symmetry related molecule that facilitated
crystallization of the G3BP2 isoform.
