Work

Structural Studies of ERK2 Protein Complexes

Year: 2016

Type: book-chapter

Abstract: ERK1 and ERK2 (ERK1/2) are the primary effector kinases of the RAS-RAF-MEK-ERK signaling pathway. A variety of substrates and regulatory partners associate with ERK1/2 through distinct D-peptide- and DEF-docking sites on their kinase domains. While understanding of D-peptides that bind to ERK1/2 has become increasingly clear over the last decade, only more recently have structures of proteins interacting with other binding sites on ERK1/2 become available. PEA-15 is a 130-residue ERK1/2 regulator that engages both the D-peptide- and DEF-docking sites of ERK kinases, and directly sequesters the ERK2 activation loop in various different phosphorylation states. Here we describe the methods used to derive crystallization-grade complexes of ERK2-PEA-15, which may also be adapted for other regulators that associate with the activation loop of ERK1/2.

Source: Methods in molecular biology

DOI: 10.1007/978-1-4939-6424-6_4

Authors: Johannes F. Weijman, Stefan J. Riedl, Peter D. Mace

Institutions: University of Otago, Sanford Burnham Prebys Medical Discovery Institute

Language: English

Topic: Protein Kinase Regulation and GTPase Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Funders: National Institute on Alcohol Abuse and Alcoholism, National Cancer Institute

Awards: Structure and function of BCAR1 and BCAR3 association in breast cancer malignancy, The Mechanism of DISC Formation