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

J. Biol. Chem., Vol. 280, Issue 12, 11347-11351, March 25, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/12/11347    most recent M414607200v1 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 Kim, J.-I. Articles by Lee, J.-O. Search for Related Content PubMed PubMed Citation Articles by Kim, J.-I. Articles by Lee, J.-O. Related Collections Papers Of The Week Social Bookmarking                      What's this?

Crystal Structure of CD14 and Its Implications for Lipopolysaccharide Signaling^*

Jung-In Kim, Chang Jun Lee, Mi Sun Jin, Cherl-Ho Lee, Sang-Gi Paik¶, Hayyoung Lee||**, and Jie-Oh Lee

From the Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea, Graduate School of Biotechnology, Korea University, Seoul 136-701, Korea, ^¶Department of Biology, School of Biosciences and Biotechnologies, and ^||Institute of Biotechnology, Chungnam National University, Daejeon 305-701, Korea

Lipopolysaccharide, the endotoxin of Gram-negative bacteria, induces extensive immune responses that can lead to fatal septic shock syndrome. The core receptors recognizing lipopolysaccharide are CD14, TLR4, and MD-2. CD14 binds to lipopolysaccharide and presents it to the TLR4/MD-2 complex, which initiates intracellular signaling. In addition to lipopolysaccharide, CD14 is capable of recognizing a few other microbial and cellular products. Here, we present the first crystal structure of CD14 to 2.5 Å resolution. A large hydrophobic pocket was found on the NH₂-terminal side of the horseshoe-like structure. Previously identified regions involved in lipopolysaccharide binding map to the rim and bottom of the pocket indicating that the pocket is the main component of the lipopolysaccharide-binding site. Mutations that interfere with lipopolysaccharide signaling but not with lipopolysaccharide binding are also clustered in a separate area near the pocket. Ligand diversity of CD14 could be explained by the generous size of the pocket, the considerable flexibility of the rim of the pocket, and the multiplicity of grooves available for ligand binding.

Received for publication, December 27, 2004 , and in revised form, January 6, 2005.

The atomic coordinates and structure factors (code 1WWL) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by Functional Proteomics Program M102KM010017 from the Ministry of Science of Korea and by Korea Research Foundation Grant KRF-2000-005-D00004). 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.

This article was selected as a Paper of the Week.

^** To whom correspondence may be addressed. Tel.: 82-42-821-7533; Fax: 82-42-822-9690; E-mail: hlee{at}cnu.ac.kr. To whom correspondence may be addressed. Tel.: 82-42-869-2839; Fax: 82-42-869-5839; E-mail: jieoh.lee{at}kaist.ac.kr.

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

This article has been cited by other articles:

				T. Frey and A. De Maio The Antifungal Agent Itraconazole Induces the Accumulation of High Mannose Glycoproteins in Macrophages J. Biol. Chem., June 19, 2009; 284(25): 16882 - 16890. [Abstract] [Full Text] [PDF]

				T. Roger, C. Froidevaux, D. Le Roy, M. K. Reymond, A.-L. Chanson, D. Mauri, K. Burns, B. M. Riederer, S. Akira, and T. Calandra Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4 PNAS, February 17, 2009; 106(7): 2348 - 2352. [Abstract] [Full Text] [PDF]

				T. Yoshimura and J. J. Oppenheim Chemerin reveals its chimeric nature J. Exp. Med., September 29, 2008; 205(10): 2187 - 2190. [Abstract] [Full Text] [PDF]

				K. L. Lloyd-Jones, M. M. Kelly, and P. Kubes Varying Importance of Soluble and Membrane CD14 in Endothelial Detection of Lipopolysaccharide J. Immunol., July 15, 2008; 181(2): 1446 - 1453. [Abstract] [Full Text] [PDF]

				M. Gangloff, A. Murali, J. Xiong, C. J. Arnot, A. N. Weber, A. M. Sandercock, C. V. Robinson, R. Sarisky, A. Holzenburg, C. Kao, et al. Structural Insight into the Mechanism of Activation of the Toll Receptor by the Dimeric Ligand Spatzle J. Biol. Chem., May 23, 2008; 283(21): 14629 - 14635. [Abstract] [Full Text] [PDF]

				K. A. Daly, C. Lefevre, K. Nicholas, E. Deane, and P. Williamson CD14 and TLR4 are expressed early in tammar (Macropus eugenii) neonate development J. Exp. Biol., April 15, 2008; 211(8): 1344 - 1351. [Abstract] [Full Text] [PDF]

				J. Meng, P. Parroche, D. T. Golenbock, and C. J. McKnight The Differential Impact of Disulfide Bonds and N-Linked Glycosylation on the Stability and Function of CD14 J. Biol. Chem., February 8, 2008; 283(6): 3376 - 3384. [Abstract] [Full Text] [PDF]

				A. Teghanemt, P. Prohinar, T. L. Gioannini, and J. P. Weiss Transfer of Monomeric Endotoxin from MD-2 to CD14: CHARACTERIZATION AND FUNCTIONAL CONSEQUENCES J. Biol. Chem., December 14, 2007; 282(50): 36250 - 36256. [Abstract] [Full Text] [PDF]

				F. Wu, N. Vij, L. Roberts, S. Lopez-Briones, S. Joyce, and S. Chakravarti A Novel Role of the Lumican Core Protein in Bacterial Lipopolysaccharide-induced Innate Immune Response J. Biol. Chem., September 7, 2007; 282(36): 26409 - 26417. [Abstract] [Full Text] [PDF]

				W.-F. Fang, J. H. Cho, Q. He, M.-C. Lin, C.-C. Wu, N. F. Voelkel, and I. S. Douglas Lipid A fraction of LPS induces a discrete MAPK activation in acute lung injury Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L336 - L344. [Abstract] [Full Text] [PDF]

				U. Ohto, K. Fukase, K. Miyake, and Y. Satow Crystal Structures of Human MD-2 and Its Complex with Antiendotoxic Lipid IVa Science, June 15, 2007; 316(5831): 1632 - 1634. [Abstract] [Full Text] [PDF]

				T. L. Gioannini, A. Teghanemt, D. Zhang, P. Prohinar, E. N. Levis, R. S. Munford, and J. P. Weiss Endotoxin-binding Proteins Modulate the Susceptibility of Bacterial Endotoxin to Deacylation by Acyloxyacyl Hydrolase J. Biol. Chem., March 16, 2007; 282(11): 7877 - 7884. [Abstract] [Full Text] [PDF]

				H. M. Kim, S. C. Oh, K. J. Lim, J. Kasamatsu, J. Y. Heo, B. S. Park, H. Lee, O. J. Yoo, M. Kasahara, and J.-O. Lee Structural Diversity of the Hagfish Variable Lymphocyte Receptors J. Biol. Chem., March 2, 2007; 282(9): 6726 - 6732. [Abstract] [Full Text] [PDF]

				L. E. Mansson, P. Kjall, S. Pellett, G. Nagy, R. A. Welch, F. Backhed, T. Frisan, and A. Richter-Dahlfors Role of the Lipopolysaccharide-CD14 Complex for the Activity of Hemolysin from Uropathogenic Escherichia coli Infect. Immun., February 1, 2007; 75(2): 997 - 1004. [Abstract] [Full Text] [PDF]

				S. P. Wiertsema, S.-K. Khoo, G. Baynam, R. H. Veenhoven, I. A. Laing, G. A. Zielhuis, G. T. Rijkers, J. Goldblatt, P. N. LeSouef, and E. A. M. Sanders Association of CD14 Promoter Polymorphism with Otitis Media and Pneumococcal Vaccine Responses. Clin. Vaccine Immunol., August 1, 2006; 13(8): 892 - 897. [Abstract] [Full Text] [PDF]

				K. Miyake Invited review: Roles for accessory molecules in microbial recognition by Toll-like receptors Innate Immunity, August 1, 2006; 12(4): 195 - 204. [Abstract] [PDF]

				C. R. H. Raetz, T. A. Garrett, C. M. Reynolds, W. A. Shaw, J. D. Moore, D. C. Smith Jr., A. A. Ribeiro, R. C. Murphy, R. J. Ulevitch, C. Fearns, et al. Kdo2-Lipid A of Escherichia coli, a defined endotoxin that activates macrophages via TLR-4 J. Lipid Res., May 1, 2006; 47(5): 1097 - 1111. [Abstract] [Full Text] [PDF]

				X. Wang, S. C. McGrath, R. J. Cotter, and C. R. H. Raetz Expression Cloning and Periplasmic Orientation of the Francisella novicida Lipid A 4'-Phosphatase LpxF J. Biol. Chem., April 7, 2006; 281(14): 9321 - 9330. [Abstract] [Full Text] [PDF]

				G. Hajishengallis, P. Ratti, and E. Harokopakis Peptide Mapping of Bacterial Fimbrial Epitopes Interacting with Pattern Recognition Receptors J. Biol. Chem., November 25, 2005; 280(47): 38902 - 38913. [Abstract] [Full Text] [PDF]

				J. Koraha, N. Tsuneyoshi, M. Kimoto, J.-F. Gauchat, H. Nakatake, and K. Fukudome Comparison of Lipopolysaccharide-Binding Functions of CD14 and MD-2 Clin. Vaccine Immunol., November 1, 2005; 12(11): 1292 - 1297. [Abstract] [Full Text] [PDF]

				J. Choe, M. S. Kelker, and I. A. Wilson Crystal Structure of Human Toll-Like Receptor 3 (TLR3) Ectodomain Science, July 22, 2005; 309(5734): 581 - 585. [Abstract] [Full Text] [PDF]