The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
A Plug Release Mechanism for Membrane Permeation by MLKL
Open accessAbstract
SUMMARY MLKL is crucial for necroptosis, permeabilizing membranes through its N-terminal region upon phosphorylation of its kinase-like domain by RIP3. However, the mechanism underlying membrane permeabilization is unknown. The solution structure of the MLKL N-terminal region determined by NMR spectroscopy reveals a four-helix bundle with an additional helix at the top that is likely key for MLKL function, and a sixth, C-terminal helix that interacts with the top helix and with a poorly packed interface within the four-helix bundle. Fluorescence spectroscopy measurements indicate that much of the four-helix bundle inserts into membranes, but not the C-terminal helix. Moreover, we find that the four-helix bundle is sufficient to induce liposome leakage and that the C-terminal helix inhibits this activity. These results suggest that the four-helix bundle mediates membrane breakdown during necroptosis and that the sixth helix acts as a plug that prevents opening of the bundle and is released upon RIP3 phosphorylation.
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Protein backbone angle restraints from searching a database for chemical shift and sequence homology
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Molecular mechanisms of necroptosis: an ordered cellular explosion
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Self-citationIdentification of RIP1 kinase as a specific cellular target of necrostatins
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RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis
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The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism
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Cited by
Necroptosis and its role in inflammation
Pasparakis, M., & Vandenabeele, P. (2015) · Nature · doi:10.1038/nature14191 · Cited by 2,148
GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death
Sborgi, L., Rühl, S., Mulvihill, E., Pipercevic, J., Heilig, R., Stahlberg, H., Farady, C. J., Müller, D. J., Broz, P., & Hiller, S. (2016) · The EMBO Journal · doi:10.15252/embj.201694696 · Cited by 1,152
A major role for ferroptosis in Mycobacterium tuberculosis –induced cell death and tissue necrosis
Amaral, E. P., Costa, D. L., Namasivayam, S., Riteau, N., Kamenyeva, O., Mittereder, L., Mayer-Barber, K. D., Andrade, B. B., & Sher, A. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20181776 · Cited by 464
Necroptosis activation in Alzheimer's disease
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Metadata
- Authors
- Su, L., Quade, B., Wang, H., Sun, L., Wang, X., & Rizo, J.
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 22
- Issue
- 10
- Pages
- 1489-1500
- ISSN
- 0969-2126 (ISSN-L)
- OpenAlex
- W2056303166
- Cited by
- 224
- References
- 11
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- bronze
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