Universität zu Köln

Yang, Xinru, Yang, Fan, Wang, Weiguang, Lin, Guangzhong, Hu, Zehan ORCID: 0000-0002-4648-5301, Han, Zhifu, Qi, Yijun, Zhang, Liman, Wang, Jiawei, Sui, Sen-Fang ORCID: 0000-0001-5253-2592 and Chai, Jijie (2018). Structural basis for specific flagellin recognition by the NLR protein NAIP5. Cell Res., 28 (1). S. 35 - 48. LONDON: NATURE PUBLISHING GROUP. ISSN 1748-7838

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Abstract

The nucleotide-binding domain-and leucine-rich repeat (LRR)-containing proteins (NLRs) function as intracellular immune receptors to detect the presence of pathogen-or host-derived signals. The mechanisms of how NLRs sense their ligands remain elusive. Here we report the structure of a bacterial flagellin derivative in complex with the NLR proteins NAIP5 and NLRC4 determined by cryo-electron microscopy at 4.28 angstrom resolution. The structure revealed that the flagellin derivative forms two parallel helices interacting with multiple domains including BIR1 and LRR of NAIP5. Binding to NAIP5 results in a nearly complete burial of the flagellin derivative, thus stabilizing the active conformation of NAIP5. The extreme C-terminal side of the flagellin is anchored to a sterically constrained binding pocket of NAIP5, which likely acts as a structural determinant for discrimination of different bacterial flagellins by NAIP5, a notion further supported by biochemical data. Taken together, our results shed light on the molecular mechanisms underlying NLR ligand perception.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Yang, Xinru UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Fan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Weiguang UNSPECIFIED UNSPECIFIED UNSPECIFIED Lin, Guangzhong UNSPECIFIED UNSPECIFIED UNSPECIFIED Hu, Zehan UNSPECIFIED orcid.org/0000-0002-4648-5301 UNSPECIFIED Han, Zhifu UNSPECIFIED UNSPECIFIED UNSPECIFIED Qi, Yijun UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhang, Liman UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Jiawei UNSPECIFIED UNSPECIFIED UNSPECIFIED Sui, Sen-Fang UNSPECIFIED orcid.org/0000-0001-5253-2592 UNSPECIFIED Chai, Jijie UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-200152
DOI:	10.1038/cr.2017.148
Journal or Publication Title:	Cell Res.
Volume:	28
Number:	1
Page Range:	S. 35 - 48
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1748-7838
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CRYO-EM STRUCTURE; INNATE IMMUNE DETECTION; BEAM-INDUCED MOTION; BACTERIAL LIGANDS; INFLAMMASOME RECEPTORS; GASDERMIN D; SECRETION; ACTIVATION; INTERLEUKIN-1-BETA; CASPASE-1 Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20015