title: A 1.7A structure of Fve, a member of the new fungal immunomodulatory protein family.
abstract: Fve, a major fruiting body protein from Flammulina velutipes, a mushroom possessing immunomodulatory activity, stimulates lymphocyte mitogenesis, suppresses systemic anaphylaxis reactions and edema, enhances transcription of IL-2, IFN-gamma and TNF-alpha, and hemagglutinates red blood cells. It appears to be a lectin with specificity for complex cell-surface carbohydrates. Fve is a non-covalently linked homodimer containing no Cys, His or Met residues. It shares sequence similarity only to the other fungal immunomodulatory proteins (FIPs) LZ-8, Gts, Vvo and Vvl, all of unknown structure. The 1.7A structure of Fve solved by single anomalous diffraction of NaBr-soaked crystals is novel: each monomer consists of an N-terminal alpha-helix followed by a fibronectin III (FNIII) fold. The FNIII fold is the first instance of "pseudo-h-type" topology, a transition between the seven beta-stranded s-type and the eight beta-stranded h-type topologies. The structure suggests that dimerization, critical for the activity of FIPs, occurs by 3-D domain swapping of the N-terminal helices and is stabilized predominantly by hydrophobic interactions. The structure of Fve is the first in this lectin family to be reported, and the first of an FNIII domain-containing protein of fungal origin.
authors.affiliation: Genome Institute of Singapore, 117528 Singapore, Singapore.
authors.forename: Palasingam
authors.initials: P
authors.lastname: Paaventhan
authors.forename: Jeremiah S
authors.initials: JS
authors.lastname: Joseph
authors.forename: See Voon
authors.initials: SV
authors.lastname: Seow
authors.forename: Shai
authors.initials: S
authors.lastname: Vaday
authors.forename: Howard
authors.initials: H
authors.lastname: Robinson
authors.forename: Kaw Yan
authors.initials: KY
authors.lastname: Chua
authors.forename: Prasanna R
authors.initials: PR
authors.lastname: Kolatkar
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000363:Agaricales / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D005656:Fungal Proteins / Q000737:chemistry*; D008958:Models, Molecular; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: D000276:Adjuvants, Immunologic; D005656:Fungal Proteins