Proteinpeptide complex crystallization: a case study on the ERK2 mitogen-activated protein kinase

Gógl, Gergő and Törő, Imre and Reményi, Attila (2013) Proteinpeptide complex crystallization: a case study on the ERK2 mitogen-activated protein kinase. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 69. pp. 486-489. ISSN 0907-4449

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Abstract

Linear motifs normally bind with only medium binding affinity (Kd of approximate to 0.110 mu M) to shallow protein-interaction surfaces on their binding partners. The crystallization of proteins in complex with linear motif-containing peptides is often challenging because the energy gained upon crystal packing between symmetry mates in the crystal may be on a par with the binding energy of the proteinpeptide complex. Furthermore, for extracellular signal-regulated kinase 2 (ERK2) the proteinpeptide docking surface is comprised of a small hydrophobic surface patch that is often engaged in the crystal packing of apo ERK2 crystals. Here, a rational surface-engineering approach is presented that involves mutating protein surface residues that are distant from the peptide-binding ERK2 docking groove to alanines. These ERK2 surface mutations decrease the chance of `unwanted' crystal packing of ERK2 and the approach led to the structure determination of ERK2 in complex with new docking peptides. These findings highlight the importance of negative selection in crystal engineering for weakly binding proteinpeptide complexes.

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