Biopolymers. 2026 Sep;117(5):e70120. doi: 10.1002/bip.70120.
ABSTRACT
The biological function of intrinsically disordered proteins is frequently coupled to short linear motifs, which serve as protein binding sites. This goes often hand in hand with local transient structural element formation. The intrinsically disordered C-terminal region of the multi-site docking protein Grb2-associated binder 1 (Gab1) contains several well-characterized phosphotyrosine pairs, whereas the Tyr162 and Tyr183 epitopes have remained practically unstudied. Here, we combine computational prediction, circular dichroism and high-resolution NMR spectroscopy (chemical shift and relaxation analyses) to structurally characterize a Gab1 fragment containing residues 142-203. The here determined NMR structure shows an α-helix for residues Pro180 to Ile187, with Tyr183 positioned centrally, while all other parts of the fragment, including the region around Tyr162, are disordered. This helical conformation is maintained upon changes in pH, variation of peptide lengths and phosphorylation status. The inherent helix around Tyr183 distinguishes the local structural environment of Tyr162 and Tyr183 within the intrinsically disordered Gab1 tail and provides a structural framework for future studies on interaction partners and potential functional roles of this structural motif.
PMID:42549985 | PMC:PMC13435814 | DOI:10.1002/bip.70120