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PDBsum entry 2msv
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Membrane protein
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PDB id
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2msv
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References listed in PDB file
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Key reference
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Title
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A plug release mechanism for membrane permeation by mlkl.
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Authors
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L.Su,
B.Quade,
H.Wang,
L.Sun,
X.Wang,
J.Rizo.
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Ref.
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Structure, 2014,
22,
1489-1500.
[DOI no: ]
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PubMed id
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Abstract
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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 nuclear magnetic resonance
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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