Structure-function analysis of human stomatin: A mutation study

Stefanie Rungaldier, Ellen Umlauf, Mario Mairhofer, Ulrich Salzer, Christoph Thiele, Rainer Prohaska

Research output: Contribution to journalArticle

28 Citations (Scopus)


Stomatin is an ancient, widely expressed, oligomeric, monotopic membrane protein that is associated with cholesterol-rich membranes/lipid rafts. It is part of the SPFH superfamily including stomatin-like proteins, prohibitins, flotillin/reggie proteins, bacterial HflK/C proteins and erlins. Biochemical features such as palmitoylation, oligomerization, and hydrophobic “hairpin” structure show similarity to caveolins and other integral scaffolding proteins. Recent structure analyses of the conserved PHB/SPFH domain revealed amino acid residues and subdomains that appear essential for the structure and function of stomatin. To test the significance of these residues and domains, we exchanged or deleted them, expressed respective GFP-tagged mutants, and studied their subcellular localization, molecular dynamics and biochemical properties. We show that stomatin is a cholesterol binding protein and that at least two domains are important for the association with cholesterol-rich membranes. The conserved, prominent coiled-coil domain is necessary for oligomerization, while association with cholesterol-rich membranes is also involved in oligomer formation. FRAP analyses indicate that the C-terminus is the dominant entity for lateral mobility and binding site for the cortical actin cytoskeleton.
Original languageEnglish
Article numbere0178646
Pages (from-to)e0178646
Number of pages24
JournalPLoS ONE
Issue number6
Publication statusPublished - Jun 2017


  • Animals
  • COS Cells
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cholesterol/metabolism
  • Green Fluorescent Proteins/genetics
  • Humans
  • Membrane Proteins/chemistry
  • Molecular Dynamics Simulation
  • Mutation
  • Protein Binding
  • Structure-Activity Relationship
  • Subcellular Fractions/metabolism
  • Prohibitins


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