Research ArticleStructural Biology

Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove

Sci. Signal.  09 Oct 2012:
Vol. 5, Issue 245, pp. ra74
DOI: 10.1126/scisignal.2003004

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Docking with the Right Partner

The mitogen-activated protein kinases (MAPKs) participate in diverse biological processes, such as inflammation and cellular proliferation, and can be divided into the c-Jun N-terminal kinase (JNK), p38, and extracellular signal–regulated kinase (ERK) families. Potential binding partners have short linear “docking” motifs (7 to 17 amino acids) with a loosely defined consensus sequence, and these motifs associate with docking grooves in MAPKs. The docking grooves in the different MAPK families are quite similar in sequence. Garai et al. uncovered the structural features of the docking motifs that enable MAPKs to discriminate between potential binding partners. They used this information to manipulate the specificity of peptides corresponding to docking motifs found in MAPK binding partners—for example, a JNK1-specific peptide was altered so that it also bound to p38α and ERK2. Furthermore, they designed artificial peptides with engineered specificities to a particular MAPK or set of MAPKs. These results provide insight into how MAPKs differentiate between seemingly similar binding partners and could be used to disrupt a specific MAPK binding partner interaction in a targeted fashion.