Protein-peptide complex crystallization: A case study on the ERK2 mitogen-activated protein kinase

Gergo Gógl, Imre Töro, A. Reményi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Linear motifs normally bind with only medium binding affinity (K d of ∼0.1-10 μM) 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 protein-peptide complex. Furthermore, for extracellular signal-regulated kinase 2 (ERK2) the protein-peptide 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 protein-peptide complexes.

Original languageEnglish
Pages (from-to)486-489
Number of pages4
JournalActa Crystallographica Section D: Biological Crystallography
Volume69
Issue number3
DOIs
Publication statusPublished - Mar 2013

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Mitogen-Activated Protein Kinase 1
Crystallization
Mitogen-Activated Protein Kinases
Peptides
Proteins
Carrier Proteins
Membrane Proteins
Alanine
Mutation

Keywords

  • ERK2
  • linear motifs
  • protein-peptide complexes
  • surface engineering

ASJC Scopus subject areas

  • Structural Biology

Cite this

Protein-peptide complex crystallization : A case study on the ERK2 mitogen-activated protein kinase. / Gógl, Gergo; Töro, Imre; Reményi, A.

In: Acta Crystallographica Section D: Biological Crystallography, Vol. 69, No. 3, 03.2013, p. 486-489.

Research output: Contribution to journalArticle

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