A 1.7 Å structure of Fve, a member of the new fungal immunomodulatory protein family

Palasingam Paaventhan, Jeremiah S. Joseph, See Voon Seow, Shai Vaday, Howard Robinson, Kaw Yan Chua, Prasanna Kolatkar

Research output: Contribution to journalArticle

68 Citations (Scopus)

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-γ and TNF-α, 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. 7Å structure of Fve solved by single anomalous diffraction of NaBr-soaked crystals is novel: each monomer consists of an N-terminal α-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 β-stranded s-type and the eight β-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.

Original languageEnglish
Pages (from-to)461-470
Number of pages10
JournalJournal of Molecular Biology
Volume332
Issue number2
DOIs
Publication statusPublished - 12 Sep 2003
Externally publishedYes

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Keywords

  • 3-D domain swapping
  • FNIII fold
  • Fungal immunomodulatory protein
  • Lectin
  • Pseudo-h-topology

ASJC Scopus subject areas

  • Virology

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