2msv

Publication Abstract from PubMed

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.

A Plug Release Mechanism for Membrane Permeation by MLKL.,Su L, Quade B, Wang H, Sun L, Wang X, Rizo J Structure. 2014 Oct 7;22(10):1489-500. doi: 10.1016/j.str.2014.07.014. Epub 2014 , Sep 11. PMID:25220470^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.