HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 23, 15825-15833, June 6, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/23/15825    most recent M800542200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murali, A. Articles by Kao, C. C. Search for Related Content PubMed PubMed Citation Articles by Murali, A. Articles by Kao, C. C. Social Bookmarking                      What's this?

Structure and Function of LGP2, a DEX(D/H) Helicase That Regulates the Innate Immunity Response^*

Ayaluru Murali¹, Xiaojun Li¹, C. T. Ranjith-Kumar, Kanchan Bhardwaj, Andreas Holzenburg, Pingwei Li, and C. Cheng Kao²

From the Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843 and the Microscopy and Imaging Center and Department of Biology, Texas A&M University, College Station, Texas 77843

RNA recognition receptors are important for detection of and response to viral infections. RIG-I and MDA5 are cytoplasmic DEX(D/H) helicase proteins that can induce signaling in response to RNA ligands, including those from viral infections. LGP2, a homolog of RIG-I and MDA5 without the caspase recruitment domain required for signaling, plays an important role in modulating signaling by MDA5 and RIG-I, presumably through heterocomplex formation and/or by serving as a sink for RNAs. Here we demonstrate that LGP2 can be coexpressed with RIG-I to inhibit activation of the NF-B reporter expression and that LGP2 protein produced in insect cells can bind both single- and double-stranded RNA (dsRNA), with higher affinity and cooperativity for dsRNA. Electron microscopy and image reconstruction were used to determine the shape of the LGP2 monomer in the absence of dsRNA and of the dimer complexed to a 27-bp dsRNA. LGP2 has striking structural similarity to the helicase domain of the superfamily 2 DNA helicase, Hef.

Received for publication, January 22, 2008 , and in revised form, March 28, 2008.

^* This work was supported, in whole or in part, by National Institutes of Health Grant 1RO1AI073335 from NIAID. This work was also supported by Centocor Inc. Grant CRA-Kao2007. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1 and 2.

¹ Both authors contributed equally to this work.

² To whom correspondence should be addressed. Tel.: 979-458-2235; Fax: 979-845-9274; E-mail: ckao{at}tamu.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				X. Li, C. T. Ranjith-Kumar, M. T. Brooks, S. Dharmaiah, A. B. Herr, C. Kao, and P. Li The RIG-I-like Receptor LGP2 Recognizes the Termini of Double-stranded RNA J. Biol. Chem., May 15, 2009; 284(20): 13881 - 13891. [Abstract] [Full Text] [PDF]

				D. Bamming and C. M. Horvath Regulation of Signal Transduction by Enzymatically Inactive Antiviral RNA Helicase Proteins MDA5, RIG-I, and LGP2 J. Biol. Chem., April 10, 2009; 284(15): 9700 - 9712. [Abstract] [Full Text] [PDF]

				D. A. Pippig, J. C. Hellmuth, S. Cui, A. Kirchhofer, K. Lammens, A. Lammens, A. Schmidt, S. Rothenfusser, and K.-P. Hopfner The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA Nucleic Acids Res., April 1, 2009; 37(6): 2014 - 2025. [Abstract] [Full Text] [PDF]

				C. T. Ranjith-Kumar, A. Murali, W. Dong, D. Srisathiyanarayanan, R. Vaughan, J. Ortiz-Alacantara, K. Bhardwaj, X. Li, P. Li, and C. C. Kao Agonist and Antagonist Recognition by RIG-I, a Cytoplasmic Innate Immunity Receptor J. Biol. Chem., January 9, 2009; 284(2): 1155 - 1165. [Abstract] [Full Text] [PDF]

				T. Saito and M. Gale Jr. Differential recognition of double-stranded RNA by RIG-I-like receptors in antiviral immunity J. Exp. Med., July 7, 2008; 205(7): 1523 - 1527. [Abstract] [Full Text] [PDF]