NLRP6 Self-assembles into a Linear Molecular Platform Following LPS Binding and ATP Stimulation

Overview

Journal Sci Rep

Specialty Science

Date 2020 Jan 15

PMID 31932628

Citations 19

Authors

Fangwei Leng

Hang Yin

Siying Qin

Kai Zhang

Yukun Guan

Run Fang

Honglei Wang

Guohui Li

Zhengfan Jiang

Fei Sun

Da-Cheng Wang

Can Xie

Affiliations

Soon will be listed here.

Abstract

NOD-like receptors (NLRs) localize in the cytosol to recognize intracellular pathogen products and initialize the innate immune response. However, the ligands and ligand specificity of many NLRs remain unclear. One such NLR, NLRP6, plays an important role in maintaining intestinal homeostasis and protecting against various intestinal diseases such as colitis and intestinal tumorigenesis. Here, we show that the major component of the outer membrane of gram-negative bacteria, lipopolysaccharide (LPS), binds NLRP6 directly and induces global conformational change and dimerization. Following stimulation by ATP, the NLRP6 homodimer can further assemble into a linear molecular platform, and ASC is recruited to form higher molecular structures, indicative of a step-by-step activation mechanism. Our study sheds light on the mystery of LPS-induced inflammasome initiation, reveals the architecture and structural basis of potential pre-inflammasome, and suggests a novel molecular assembly pattern for immune receptors.

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