Work

Rat ERK2 E320K

Year: 2019

Type: dataset

Abstract: , only ERK2 D-N displays a significant gain of function, revealing mutation-specific phenotypes. The crystal structure of ERK2 D-N is indistinguishable from that of wild-type protein, yet this mutant displays increased thermal stability. In contrast, the crystal structure of ERK2 E-K reveals profound structural changes, including disorder in the CD site and exposure of the activation loop phosphorylation sites, which likely account for the decreased thermal stability of the protein. These contiguous mutations in the CD site of ERK2 are both required for docking interactions but lead to unpredictably different functional outcomes. Our results suggest that the CD site is in an energetically strained configuration, and this helps drive conformational changes at distal sites on ERK2 during docking interactions.

Source: Worldwide Protein Data Bank

DOI: 10.2210/pdb6ots/pdb

Authors: C.A. Taylor, K.W. Cormier, Y.-C. Juang, E.J. Goldsmith, M.H. Cobb

Institutions: The University of Texas Southwestern Medical Center, Princeton University

Language: English

Topic: Protein Kinase Regulation and GTPase Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Cancer Institute

Awards: Insulin-Regulated MAP Kinase Pathways, Activating mutations in MEK: from molecules to morphologies, UT Southwestern Medical Center Simmons Comprehensive Cancer Center

OpenAlex ID: W2956797447

Cites: 61

Cited by: 18

Related to: 20