title: FAM3B PANDER and FAM3C ILEI represent a distinct class of signaling molecules with a non-cytokine-like fold.
abstract: The FAM3 superfamily is predicted to contain classical four-helix bundle cytokines, featuring a typical up-up-down-down fold. Two members of FAM3 have been extensively studied. FAM3B PANDER has been shown to regulate glucose homeostasis and β cell function, whereas the homologous FAM3C ILEI has been shown to be involved in epithelial-mesenchymal transition and cancer. Here, we present a three-dimensional structure of a FAM3 protein, murine PANDER. Contrary to previous suggestions, PANDER exhibits a globular β-β-α fold. The structure is composed of two antiparallel β sheets lined by three short helices packing to form a highly conserved water-filled cavity. The fold shares no relation to the predicted four-helix cytokines but is conserved throughout the FAM3 superfamily. The available biological data and the unexpected new fold indicate that FAM3 PANDER and ILEI could represent a new structural class of signaling molecules, with a different mode of action compared to the traditional four-helix bundle cytokines.
authors: Structure and Biophysics, Discovery Sciences, AstraZeneca, Mölndal 431-83, Sweden.
authors: Patrik
authors: P
authors: Johansson
authors: Jenny
authors: J
authors: Bernström
authors: Tracy
authors: T
authors: Gorman
authors: Linda
authors: L
authors: Oster
authors: Stefan
authors: S
authors: Bäckström
authors: Fritz
authors: F
authors: Schweikart
authors: Bingze
authors: B
authors: Xu
authors: Yafeng
authors: Y
authors: Xue
authors: Lovisa Holmberg
authors: LH
authors: Schiavone
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D016207:Cytokines / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013499:Surface Properties
chemical_list: D016207:Cytokines; C488587:Fam3c protein, mouse; D009363:Neoplasm Proteins; C504749:PANDER protein, mouse