The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Structural Insights into RIP3-Mediated Necroptotic Signaling
Open accessAbstract
RIP3 is an essential upstream kinase in necroptosis. The pseudokinase MLKL functions as a substrate of RIP3 to mediate downstream signaling. The molecular mechanism by which RIP3 recognizes and phosphorylates MLKL remains unknown. Here, we report the crystal structures of the mouse RIP3 kinase domain, the MLKL kinase-like domain, and a binary complex between the two. Both RIP3 and MLKL adopt the canonical kinase fold. Free RIP3 exists in an active conformation, whereas MLKL-bound RIP3 is stabilized by AMP-PNP to adopt an inactive conformation. The formation of the RIP3-MLKL complex, involving their respective N- and C-lobes, is accompanied by pronounced conformational changes of the αC helix and activation loop in RIP3 and the corresponding structural elements in MLKL. RIP3-mediated MLKL phosphorylation, though important for downstream signaling, is dispensable for stable complex formation between RIP3 and MLKL. Our study serves as a framework for mechanistic understanding of RIP3-mediated necroptotic signaling.
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Protein Structure Comparison by Alignment of Distance Matrices
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“Search of the protein data bank using DALI (Holm and Sander, 1993) uncovered the closest entry of MLKL-bound RIP3 to be the tyrosine kinase ABL1 bound to a bisubstrate analog (Levinson et al., 2006).”
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Molecular mechanisms of necroptosis: an ordered cellular explosion
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Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
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Cited by
Regulated necrosis: the expanding network of non-apoptotic cell death pathways
Berghe, T. V., Linkermann, A., Jouan-Lanhouet, S., Walczak, H., & Vandenabeele, P. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3737 · Cited by 1,735
Regulation of tumour necrosis factor signalling: live or let die
Brenner, D., Blaser, H., & Mak, T. W. (2015) · Nature Reviews Immunology · doi:10.1038/nri3834 · Cited by 998
ESCRT-III Acts Downstream of MLKL to Regulate Necroptotic Cell Death and Its Consequences
Gong, Y.-N., Guy, C., Olauson, H., Becker, J. U., Yang, M., Fitzgerald, P., Linkermann, A., & Green, D. R. (2017) · Cell · doi:10.1016/j.cell.2017.03.020 · Cited by 689
Initiation and execution mechanisms of necroptosis: an overview
Grootjans, S., Vanden Berghe, T., & Vandenabeele, P. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.65 · Cited by 566
Distinct roles of RIP1–RIP3 hetero- and RIP3–RIP3 homo-interaction in mediating necroptosis
Wu, X.-N., Yang, Z.-H., Wang, X.-K., Zhang, Y., Wan, H., Song, Y., Chen, X., Shao, J., & Han, J. (2014) · Cell Death & Differentiation · doi:10.1038/cdd.2014.77 · Cited by 299
Metadata
- Authors
- Xie, T., Peng, W., Yan, C., Wu, J., Gong, X., & Shi, Y.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 5
- Issue
- 1
- Pages
- 70-78
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2049587638
- Cited by
- 194
- References
- 7
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- gold
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