4H3P

Crystal structure of human ERK2 complexed with a MAPK docking peptide

Summary for 4H3P

• Entry DOI: 10.2210/pdb4h3p/pdb
• Related: 3TEI 4H3Q
• Descriptor: Mitogen-activated protein kinase 1, Ribosomal protein S6 kinase alpha-1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total)
• Functional Keywords: kinase domain, signaling, linear motif, surface mutation, transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, cytoskeleton, spindle (By similarity): P28482; Nucleus: Q15418
• Total number of polymer chains: 4
• Total formula weight: 89230.09

Authors

Gogl, G.,Toeroe, I.,Remenyi, A. (deposition date: 2012-09-14, release date: 2013-02-27, Last modification date: 2023-11-08)

Primary citation

Gogl, G.,Toeroe, I.,Remenyi, A.
Protein-peptide complex crystallization: a case study on the ERK2 mitogen-activated protein kinase
Acta Crystallogr.,Sect.D, 69:486-489, 2013

PubMed Abstract: Linear motifs normally bind with only medium binding affinity (Kd 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.

PubMed: 23519423
DOI: 10.1107/S0907444912051062

Experimental method

X-RAY DIFFRACTION (2.3 Å)