Nogo-B receptor possesses an intrinsically unstructured ectodomain and a partially folded cytoplasmic domain.
RTN4/Nogo proteins containing three isoforms have been implicated in a large and diverse spectrum of biological functions. By contrast, only two functional receptors were known for them, namely NgR binding the 66-residue ectodomain shared by all three Nogos and NgBR specifically binding Nogo-B. The 297-residue NgBR was recently identified to be essential for stimulating chemotaxis and morphogenesis of endothelial cells but its structural property still remains completely unknown. In the present study, we expressed and subsequently conducted bioinformatics, CD and NMR characterization of NgBR and its two dissected domains. Very surprisingly, our results indicate that the NgBR ectodomain is intrinsically unstructured without both secondary and tertiary structures while the cytoplasmic domain is only partially folded with secondary structures but without a tight tertiary packing. Therefore, NgBR is a very rare example showing that the entire ectodomain of a transmembrane receptor could be predominantly disordered and the results presented here may bear important implications in understanding NgBR functions in the future.
Li
Minfen
M
Department of Biological Sciences, Faculty of Science, Yong Loo Lin School of Medicine and National University of Singapore, 10 Kent Ridge Crescent, 119260, Singapore.
Song
Jianxing
J
D000595:Amino Acid Sequence; D000818:Animals; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure
C512615:Nogo-B receptor, mouse; D011956:Receptors, Cell Surface