Caspase-4 disaggregates lipopolysaccharide micelles via LPS-CARD interaction

Title
Caspase-4 disaggregates lipopolysaccharide micelles via LPS-CARD interaction
Authors
양은경정학숙이경은김소연김성호안진수황두현김민정
Keywords
Inflammatory caspase; lipopolysaccharide; caspase-4; LPS-caspase-4 interaction; CARD domain
Issue Date
2019-01
Publisher
Scientific Reports
Citation
VOL 9, NO 826-9
Abstract
Lipopolysaccharides (LPS) are a major component of the outer membrane of Gram-negative bacteria and are pathogen-associated molecular patterns recognized by the TLR4/MD2 complex that induces an inflammatory response. Recently, the cytosolic receptors caspase-4/-5/-11 that bind LPS inside the cell and trigger inflammasome activation or pyroptosis, have been identified. Despite the important roles of caspase-4 in human immune responses, few studies have investigated its biochemical characteristics and interactions with LPS. Since caspase-4 (C258A) purified from an Escherichia coli host forms aggregates, monomeric proteins including full-length caspase-4, caspase-4 (C258A), and the CARD domain of caspase-4 have been purified from the insect cell system. Here, we report the overexpression and purification of monomeric caspase-4 (C258A) and CARD domain from E. coli and demonstrate that purified caspase-4 (C258A) and CARD domain bind large LPS micelles and disaggregate them to small complexes. As the molar ratio of caspase-4 to LPS increases, the size of the caspase-4/LPS complex decreases. Our results present a new function of caspase-4 and set the stage for structural and biochemical studies, and drug discovery targeting LPS/caspase-4 interactions by establishing a facile purification method to obtain large quantities of purified caspase-4 (C258A) and the CARD domain.
URI
http://pubs.kist.re.kr/handle/201004/69007
ISSN
2045-2322
Appears in Collections:
KIST Publication > Article
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