title: The structure of the extracellular domain of the jumping translocation breakpoint protein reveals a variation of the midkine fold.
abstract: Jumping Translocation Breakpoint (JTB) is an orphan receptor that is conserved from nematodes to humans and whose gene expression in humans is strikingly upregulated in diverse types of cancers. Translocations occur frequently at the hJTB genomic locus, leading to multiple copies of a truncated JTB gene, which potentially encodes a soluble secreted ectodomain. In addition, JTB and its orthologs likely represent a unique and ancient protein family since homologs could not be identified by direct sequence comparison. In the present study, we have determined the NMR solution structure of the N-terminal ectodomain of human JTB, showing that its fold architecture is a new variant of a three-β-strand antiparallel β-meander. The JTB structure has a distant relationship to the midkine/pleiotrophin fold, particularly in the conservation of distinctive disulfide bridge patterns. The structure of this newly characterized small cysteine-rich domain suggests potential involvement of JTB in interactions with proteins or extracellular matrix and may help to uncover the elusive biological functions of this protein.
authors.affiliation: Department of Early Discovery Biochemistry, South San Francisco, CA 94080, USA.
authors.forename: Francois
authors.initials: F
authors.lastname: Rousseau
authors.forename: Borlan
authors.initials: B
authors.lastname: Pan
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Fairbrother
authors.forename: J Fernando
authors.initials: JF
authors.lastname: Bazan
authors.forename: Andreas
authors.initials: A
authors.lastname: Lingel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry; D003001:Cloning, Molecular / Q000379:methods; D016207:Cytokines / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D000078792:Midkine; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D004220:Disulfides; C407989:JTB protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C066845:pleiotrophin; D000078792:Midkine