Structure of the NLRP1 Caspase Recruitment Domain Suggests Potential Mechanisms for Its Association with Procaspase-1

Overview

Journal Proteins

Date 2013 Mar 20

PMID 23508996

Citations 37

Authors

Tengchuan Jin

James Curry

Patrick Smith

Jiansheng Jiang

T Sam Xiao

Affiliations

Soon will be listed here.

Abstract

The NLRP1 inflammasome responds to microbial challenges such as Bacillus anthracis infection and is implicated in autoimmune disease such as vitiligo. Human NLRP1 contains both an N-terminal pyrin domain (PYD) and a C-terminal caspase recruitment domain (CARD), with the latter being essential for its association with the downstream effector procaspase-1. Here we report a 2.0 Å crystal structure of the human NLRP1 CARD as a fusion with the maltose-binding protein. The structure reveals the six-helix bundle fold of the NLRP1 CARD, typical of the death domain superfamily. The charge surface of the NLRP1 CARD structure and a procaspase-1 CARD model suggests potential mechanisms for their association through electrostatic attraction.

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References

Holm L, Rosenstrom P . Dali server: conservation mapping in 3D. Nucleic Acids Res. 2010; 38(Web Server issue):W545-9. PMC: 2896194. DOI: 10.1093/nar/gkq366. View

Chen V, Arendall 3rd W, Headd J, Keedy D, Immormino R, Kapral G . MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 1):12-21. PMC: 2803126. DOI: 10.1107/S0907444909042073. View

Roy A, Kucukural A, Zhang Y . I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc. 2010; 5(4):725-38. PMC: 2849174. DOI: 10.1038/nprot.2010.5. View

Park H, Lo Y, Lin S, Wang L, Yang J, Wu H . The death domain superfamily in intracellular signaling of apoptosis and inflammation. Annu Rev Immunol. 2007; 25:561-86. PMC: 2904440. DOI: 10.1146/annurev.immunol.25.022106.141656. View

Potter J, Randall R, Taylor G . Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain. BMC Struct Biol. 2008; 8:11. PMC: 2291057. DOI: 10.1186/1472-6807-8-11. View

Jin Y, Mailloux C, Gowan K, Riccardi S, LaBerge G, Bennett D . NALP1 in vitiligo-associated multiple autoimmune disease. N Engl J Med. 2007; 356(12):1216-25. DOI: 10.1056/NEJMoa061592. View

Potterton E, Briggs P, Turkenburg M, Dodson E . A graphical user interface to the CCP4 program suite. Acta Crystallogr D Biol Crystallogr. 2003; 59(Pt 7):1131-7. DOI: 10.1107/s0907444903008126. View

Davis B, Wen H, Ting J . The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol. 2011; 29:707-35. PMC: 4067317. DOI: 10.1146/annurev-immunol-031210-101405. View

Adams P, Afonine P, Bunkoczi G, Chen V, Davis I, Echols N . PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 2):213-21. PMC: 2815670. DOI: 10.1107/S0907444909052925. View

10.

Martinon F, Burns K, Tschopp J . The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002; 10(2):417-26. DOI: 10.1016/s1097-2765(02)00599-3. View

11.

McCoy A, Grosse-Kunstleve R, Adams P, Winn M, Storoni L, Read R . Phaser crystallographic software. J Appl Crystallogr. 2009; 40(Pt 4):658-674. PMC: 2483472. DOI: 10.1107/S0021889807021206. View

12.

Qin H, Srinivasula S, Wu G, Fernandes-Alnemri T, Alnemri E, Shi Y . Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1. Nature. 1999; 399(6736):549-57. DOI: 10.1038/21124. View

13.

Otwinowski Z, Minor W . Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 1997; 276:307-26. DOI: 10.1016/S0076-6879(97)76066-X. View

14.

Faustin B, Lartigue L, Bruey J, Luciano F, Sergienko E, Bailly-Maitre B . Reconstituted NALP1 inflammasome reveals two-step mechanism of caspase-1 activation. Mol Cell. 2007; 25(5):713-24. DOI: 10.1016/j.molcel.2007.01.032. View

15.

Boyden E, Dietrich W . Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet. 2006; 38(2):240-4. DOI: 10.1038/ng1724. View

16.

Emsley P, Cowtan K . Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr. 2004; 60(Pt 12 Pt 1):2126-32. DOI: 10.1107/S0907444904019158. View

17.

Hofmann K, Bucher P, Tschopp J . The CARD domain: a new apoptotic signalling motif. Trends Biochem Sci. 1997; 22(5):155-6. DOI: 10.1016/s0968-0004(97)01043-8. View

18.

Honig B, Nicholls A . Classical electrostatics in biology and chemistry. Science. 1995; 268(5214):1144-9. DOI: 10.1126/science.7761829. View