Resting and Active States of the ERK2:HePTP Complex
Open accessAbstract
The MAP kinase ERK2 (ERK2, extracellular signal-regulated kinase 2) is regulated by numerous phosphatases that tightly control its activity. For example, the hematopoietic tyrosine phosphatase (HePTP) negatively regulates T cell activation in lymphocytes via ERK2 dephosphorylation. However, only very limited structural information is available for these biologically important complexes. Here, we use small-angle X-ray scattering combined with EROS ensemble refinement to characterize the structures of the resting and active states of ERK2:HePTP complexes. Our data show that the resting state ERK2:HePTP complex adopts a highly extended, dynamic conformation that becomes compact and ordered in the active state complex. This work experimentally demonstrates that these complexes undergo significant dynamic structural changes in solution and provides the first structural insight into an active state MAPK complex.
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The p38:HePTP complex is elongated in solution.
“This observation, coupled with SAXS experiments that showed that the p38:HePTP complex is elongated in solution and reverse titrations that allowed us to unequivocally define which HePTP residues bind p38, led to the development of new computational procedure, ensemble refinement of SAXS (EROS)-NMR.”
From Molecular basis of MAP kinase regulation (2013) · cites this paper as [71]
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- Authors
- Francis, D. M., Różycki, B., Tortajada, A., Hummer, G., Peti, W., & Page, R.
- Affiliations
- Brown University (US)
- National Institutes of Health (US)
- Corresponding author
- Page, Rebecca
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2011-10-10
- Volume
- 133
- Issue
- 43
- Pages
- 17138-17141
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- PMC
- PMC3210578
- OpenAlex
- W1991059492
- Cited by
- 32
- References
- 32
- Citations by year
- 2023: 1 · 2021: 1 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 7 · 2013: 5 · 2012: 2
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (ZIADK029033)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- ERK2, mitogen-activated protein kinase, protein complex structure, conformational dynamics, T cell activation, small-angle X-ray scattering
- MeSH terms
- Models, Molecular, X-Ray Diffraction, Protein Tyrosine Phosphatases, Mitogen-Activated Protein Kinase 1, Scattering, Small Angle
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