Electrostatic influence on IL-1 transport through the GSDMD pore.

ABSTRACT: A variety of signals, including inflammasome activation, trigger the formation of large transmembrane pores by gasdermin D (GSDMD). There are primarily two functions of the GSDMD pore, to drive lytic cell death, known as pyroptosis, and to permit the release of leaderless interleukin-1 (IL-1) family cytokines, a process that does not require pyroptosis. We are interested in the mechanism by which the GSDMD pore channels IL-1 release from living cells. Recent studies revealed that electrostatic interaction, in addition to cargo size, plays a critical role in GSDMD-dependent protein release. Here, we determined computationally that to enable electrostatic filtering against pro-IL-1β, acidic lipids in the membrane need to effectively neutralize positive charges in the membrane-facing patches

SUBMITTER: Xie WJ 

PROVIDER: S-EPMC8833203 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature