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Originally published In Press as doi:10.1074/jbc.M608471200 on December 27, 2006

J. Biol. Chem., Vol. 282, Issue 9, 6726-6732, March 2, 2007
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Structural Diversity of the Hagfish Variable Lymphocyte Receptors*Formula

Ho Min Kim{ddagger}1, Se Cheol Oh§1, Ki Jung Lim{ddagger}, Jun Kasamatsu, Jin Young Heo§, Beom Seok Park§, Hayyoung Lee||, Ook Joon Yoo{ddagger}, Masanori Kasahara, and Jie-Oh Lee§2

From the {ddagger}Department of Biological Sciences and the §Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea, the Department of Pathology, Hokkaido University School of Medicine, Sapporo 060-8638, Japan, and the ||Institute of Biotechnology, Chungnam National University, Daejeon 305-764, Korea

Variable lymphocyte receptors (VLRs) are recently discovered leucine-rich repeat (LRR) family proteins that mediate adaptive immune responses in jawless fish. Phylogenetically it is the oldest adaptive immune receptor and the first one with a non-immunoglobulin fold. We present the crystal structures of one VLR-A and two VLR-B clones from the inshore hagfish. The hagfish VLRs have the characteristic horseshoe-shaped structure of LRR family proteins. The backbone structures of their LRR modules are highly homologous, and the sequence variation is concentrated on the concave surface of the protein. The conservation of key residues suggests that our structures are likely to represent the LRR structures of the entire repertoire of jawless fish VLRs. The analysis of sequence variability, prediction of protein interaction surfaces, amino acid composition analysis, and structural comparison with other LRR proteins suggest that the hypervariable concave surface is the most probable antigen binding site of the VLR.


Received for publication, September 5, 2006 , and in revised form, November 17, 2006.

* This work was supported by grants from the 21C Functional Proteomics Project (FPR05B2-140) and the Molecular and Cellular BioDiscovery Project (2004-01729) from the Korean Ministry of Science and Technology. 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.

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

1 These authors contributed equally to this work.

2 To whom correspondence should be addressed. Tel.: 82-42-869-2839; Fax: 82-42-869-5839; E-mail: jieoh.lee{at}kaist.ac.kr.


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