Three tandem GS flexible linker

Three tandem copies of the dipeptide GS, encoding the six-residue glycine-serine linker GSGSGS. A short, flexible, hydrophilic spacer that joins two polypeptides, for example an antigenic peptide tethered to the N terminus of an MHC class II beta chain, without interfering with the function of either partner.

Length: 18 bp

Subtype: flexible_linker

Origin: Synthetic glycine-serine repeat

Characteristics

Encodes GSGSGS (6 amino acids, 18 nucleotides). Glycine lacks a side chain, which maximizes backbone conformational freedom, and serine is polar and prefers to interact with solvent rather than with the fused proteins. Six residues is within the 5 to 11 residue range common for linkers in structural studies. In the ovalbumin peptide-MHC class II I-Ad structure (PDB 2IAD) the linker electron density is not observed, consistent with a disordered, flexible segment.

Applications: Tethers antigenic peptides to the N terminus of the MHC class II beta chain for crystallography: GSGSGS linked influenza hemagglutinin, ovalbumin, CLIP and myelin basic protein peptides to I-Ad, I-Ab and I-Au. The ovalbumin peptide tethered to the I-Ad beta chain by this six-residue linker stabilized alpha-beta heterodimers.

Limitations: Optimal linker length varies case by case. A linker of nonoptimal length can let a tethered partner bind an adjacent molecule instead of its intended site, as seen with the GSGSGSGS-linked measles virus phosphoprotein and nucleocapsid peptide. The linker is not resolved in crystal structures, so it fixes no distance or orientation.

Sequence

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References

  1. Reddy Chichili et al. (2013). Linkers in the structural biology of protein–protein interactions. Protein Sci - ReddyChichili 2013 Linkers