title: Structural diversity of the hagfish variable lymphocyte receptors.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Ho Min
authors.initials: HM
authors.lastname: Kim
authors.forename: Se Cheol
authors.initials: SC
authors.lastname: Oh
authors.forename: Ki Jung
authors.initials: KJ
authors.lastname: Lim
authors.forename: Jun
authors.initials: J
authors.lastname: Kasamatsu
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Heo
authors.forename: Beom Seok
authors.initials: BS
authors.lastname: Park
authors.forename: Hayyoung
authors.initials: H
authors.lastname: Lee
authors.forename: Ook Joon
authors.initials: OJ
authors.lastname: Yoo
authors.forename: Masanori
authors.initials: M
authors.lastname: Kasahara
authors.forename: Jie-Oh
authors.initials: JO
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015321:Gene Rearrangement; D006196:Hagfishes; D007798:Lampreys; D011487:Protein Conformation; D011946:Receptors, Antigen / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D017385:Sequence Homology
chemical_list: D011946:Receptors, Antigen