Home LiteratureArticle Details
PMID: 18307765 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain.

BMC structural biology ·Vol. 8 ·2008-02-28 ·Pages 11

Potter JA, Randall RE, Taylor GL

Abstract

IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region. The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1A resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs. The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.

MeSH Terms
Adaptor Proteins, Signal Transducing/chemistry,genetics,metabolism Amino Acid Sequence Crystallography, X-Ray Humans Models, Molecular Molecular Sequence Data Myelin Basic Protein Nerve Tissue Proteins/chemistry,genetics,metabolism Protein Structure, Secondary Protein Structure, Tertiary Recombinant Fusion Proteins/chemistry,genetics,metabolism Sequence Homology, Amino Acid Transcription Factors/chemistry,genetics,metabolism
Chemicals
Adaptor Proteins, Signal Transducing MAVS protein, human MBP protein, human Myelin Basic Protein Nerve Tissue Proteins Recombinant Fusion Proteins Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Potter Jane A
Centre for Biomolecular Sciences, University of St Andrews, St Andrews, Fife, KY16 9ST, UK. jap7@st-andrews.ac.uk
Randall Richard E
Taylor Garry L
References (51)
51 references, click to expand
  1. The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes.
    Nat Struct Biol. 2003 Dec;10(12):1026-32 PMID: 14625589
  2. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity.
    Nature. 2007 Apr 19;446(7138):916-920 PMID: 17392790
  3. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2.
    Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):582-7 PMID: 17190814
  4. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3.
    Cell. 2005 Sep 9;122(5):669-82 PMID: 16125763
  5. The death domain superfamily in intracellular signaling of apoptosis and inflammation.
    Annu Rev Immunol. 2007;25:561-86 PMID: 17201679
  6. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity.
    J Immunol. 2005 Sep 1;175(5):2851-8 PMID: 16116171
  7. Use of TLS parameters to model anisotropic displacements in macromolecular refinement.
    Acta Crystallogr D Biol Crystallogr. 2001 Jan;57(Pt 1):122-33 PMID: 11134934
  8. Structure of the CED-4-CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans.
    Nature. 2005 Oct 6;437(7060):831-7 PMID: 16208361
  9. Structure and function of the interferon-beta enhanceosome.
    Cold Spring Harb Symp Quant Biol. 1998;63:609-20 PMID: 10384326
  10. Solution structure of the RAIDD CARD and model for CARD/CARD interaction in caspase-2 and caspase-9 recruitment.
    Cell. 1998 Jul 24;94(2):171-80 PMID: 9695946
  11. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses.
    Nature. 2006 May 4;441(7089):101-5 PMID: 16625202
  12. Optimal description of a protein structure in terms of multiple groups undergoing TLS motion.
    Acta Crystallogr D Biol Crystallogr. 2006 Apr;62(Pt 4):439-50 PMID: 16552146
  13. Activation of TBK1 and IKKvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity.
    J Virol. 2004 Oct;78(19):10636-49 PMID: 15367631
  14. Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex.
    Cell. 2007 Feb 9;128(3):533-46 PMID: 17289572
  15. The CCP4 suite: programs for protein crystallography.
    Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3 PMID: 15299374
  16. The Atg5 Atg12 conjugate associates with innate antiviral immune responses.
    Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14050-5 PMID: 17709747
  17. Enhanced genome annotation using structural profiles in the program 3D-PSSM.
    J Mol Biol. 2000 Jun 2;299(2):499-520 PMID: 10860755
  18. ARP/wARP and automatic interpretation of protein electron density maps.
    Methods Enzymol. 2003;374:229-44 PMID: 14696376
  19. Toll-like receptors and Type I interferons.
    J Biol Chem. 2007 May 25;282(21):15319-23 PMID: 17395581
  20. Generation of large deletion mutants from plasmid DNA.
    Biotechniques. 2004 Mar;36(3):402-4, 406 PMID: 15038154
  21. VISA is an adapter protein required for virus-triggered IFN-beta signaling.
    Mol Cell. 2005 Sep 16;19(6):727-40 PMID: 16153868
  22. Comparative protein modelling by satisfaction of spatial restraints.
    J Mol Biol. 1993 Dec 5;234(3):779-815 PMID: 8254673
  23. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures.
    J Gen Virol. 2008 Jan;89(Pt 1):1-47 PMID: 18089727
  24. Refinement of macromolecular structures by the maximum-likelihood method.
    Acta Crystallogr D Biol Crystallogr. 1997 May 1;53(Pt 3):240-55 PMID: 15299926
  25. Viruses and interferon: a fight for supremacy.
    Nat Rev Immunol. 2002 Sep;2(9):675-87 PMID: 12209136
  26. Extensive features of tight oligosaccharide binding revealed in high-resolution structures of the maltodextrin transport/chemosensory receptor.
    Structure. 1997 Aug 15;5(8):997-1015 PMID: 9309217
  27. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids.
    Nucleic Acids Res. 2007 Jul;35(Web Server issue):W375-83 PMID: 17452350
  28. Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif.
    EMBO J. 2006 Jul 26;25(14):3257-63 PMID: 16858409
  29. Crystal structure of Apaf-1 caspase recruitment domain: an alpha-helical Greek key fold for apoptotic signaling.
    J Mol Biol. 1999 Oct 29;293(3):439-47 PMID: 10543941
  30. Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization.
    Mol Cell. 1998 Jun;1(7):949-57 PMID: 9651578
  31. The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter.
    Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17264-9 PMID: 15563593
  32. Insights into binding cooperativity of MATa1/MATalpha2 from the crystal structure of a MATa1 homeodomain-maltose binding protein chimera.
    Protein Sci. 2003 Feb;12(2):306-12 PMID: 12538894
  33. MasterCARD: a priceless link to innate immunity.
    Trends Mol Med. 2006 Feb;12(2):53-6 PMID: 16406812
  34. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction.
    Nat Immunol. 2005 Oct;6(10):981-8 PMID: 16127453
  35. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates.
    Science. 2006 Nov 10;314(5801):997-1001 PMID: 17038589
  36. Coot: model-building tools for molecular graphics.
    Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32 PMID: 15572765
  37. Triggering the interferon antiviral response through an IKK-related pathway.
    Science. 2003 May 16;300(5622):1148-51 PMID: 12702806
  38. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.
    Nat Immunol. 2004 Jul;5(7):730-7 PMID: 15208624
  39. Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase.
    Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11706-11 PMID: 17600090
  40. Crystal structure of the Nod1 caspase activation and recruitment domain.
    Biochem Biophys Res Commun. 2007 Feb 2;353(1):1-5 PMID: 17173864
  41. Phaser crystallographic software.
    J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674 PMID: 19461840
  42. 5'-Triphosphate RNA is the ligand for RIG-I.
    Science. 2006 Nov 10;314(5801):994-7 PMID: 17038590
  43. Solution structure of NOD1 CARD and mutational analysis of its interaction with the CARD of downstream kinase RICK.
    J Mol Biol. 2007 Jan 5;365(1):160-74 PMID: 17054981
  44. Structural basis of procaspase-9 recruitment by the apoptotic protease-activating factor 1.
    Nature. 1999 Jun 10;399(6736):549-57 PMID: 10376594
  45. Innate immune recognition of viral infection.
    Nat Immunol. 2006 Feb;7(2):131-7 PMID: 16424890
  46. ICEBERG: a novel inhibitor of interleukin-1beta generation.
    Cell. 2000 Sep 29;103(1):99-111 PMID: 11051551
  47. Basis for a ubiquitin-like protein thioester switch toggling E1-E2 affinity.
    Nature. 2007 Jan 25;445(7126):394-8 PMID: 17220875
  48. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus.
    Nature. 2005 Oct 20;437(7062):1167-72 PMID: 16177806
  49. Inherent protein structural flexibility at the RNA-binding interface of L30e.
    J Mol Biol. 2003 Feb 28;326(4):999-1004 PMID: 12589748
  50. A docking model of key components of the DISC complex: death domain superfamily interactions redefined.
    FEBS Lett. 2001 Mar 16;492(3):171-6 PMID: 11257489
  51. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.
    Nat Immunol. 2003 May;4(5):491-6 PMID: 12692549
Article Info
Journal
BMC structural biology
Abbr.
BMC Struct Biol
ISSN
1472-6807
DOI
10.1186/1472-6807-8-11
Email
jap7@st-andrews.ac.uk
Published
2008-02-28
Epub
2008-00-28
Pages
11
Language
English
Region
England
NLM ID
101088689
PMCID
PMC2291057
Subset
IM
Grants
Wellcome Trust · 076494 · United Kingdom
External Links
PubMed source DOI: 10.1186/1472-6807-8-11 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2