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Structural Basis of Smad2 Recognition by the Smad Anchor for Receptor Activation
Abstract
The Smad proteins mediate transforming growth factor–β (TGFβ) signaling from the transmembrane serine-threonine receptor kinases to the nucleus. The Smad anchor for receptor activation (SARA) recruits Smad2 to the TGFβ receptors for phosphorylation. The crystal structure of a Smad2 MH2 domain in complex with the Smad-binding domain (SBD) of SARA has been determined at 2.2 angstrom resolution. SARA SBD, in an extended conformation comprising a rigid coil, an α helix, and a β strand, interacts with the β sheet and the three-helix bundle of Smad2. Recognition between the SARA rigid coil and the Smad2 β sheet is essential for specificity, whereas interactions between the SARA β strand and the Smad2 three-helix bundle contribute significantly to binding affinity. Comparison of the structures between Smad2 and a comediator Smad suggests a model for how receptor-regulated Smads are recognized by the type I receptors.
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Citations
Cited by
SPECIFICITY AND VERSATILITY IN TGF-β SIGNALING THROUGH SMADS
Feng, X.-H., & Derynck, R. (2005) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.022404.142018 · Cited by 1,869
Specificity, versatility, and control of TGF-β family signaling
Derynck, R., & Budi, E. H. (2019) · Science Signaling · doi:10.1126/scisignal.aav5183 · Cited by 785
Transforming Growth Factor-β1 to the Bone
Janssens, K., ten Dijke, P., Janssens, S., & Van Hul, W. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0001 · Cited by 710
The transforming growth factor-β superfamily of receptors
de Caestecker, M. (2004) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2003.10.004 · Cited by 464
Structural insights into BMP receptors: Specificity, activation and inhibition
Yadin, D., Knaus, P., & Mueller, T. D. (2016) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2015.11.005 · Cited by 221
Metadata
- Authors
- Wu, G., Chen, Y.-G., Ozdamar, B., Gyuricza, C. A., Chong, P. A., Wrana, J. L., Massagué, J., & Shi, Y.
- Venue
- Science
- Published
- 2000-01-07
- Volume
- 287
- Issue
- 5450
- Pages
- 92-97
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2036472425
- Cited by
- 298
- References
- 0
- FWCI
- 8.79
- Type
- journal article
- Language
- en
- Open access
- closed
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- Wu, G., Chen, Y.-G., Ozdamar, B., Gyuricza, C. A., Chong, P. A., Wrana, J. L., Massagué, J., & Shi, Y. (2000). Structural Basis of Smad2 Recognition by the Smad Anchor for Receptor Activation. Science. https://doi.org/10.1126/science.287.5450.92
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