Crystal structure of a core domain of stomatin from Pyrococcus horikoshii Illustrates a novel trimeric and coiled-coil fold

J Mol Biol. 2008 Feb 22;376(3):868-78. doi: 10.1016/j.jmb.2007.12.024. Epub 2008 Jan 8.

Abstract

Stomatin is a major integral membrane protein of human erythrocytes, the absence of which is associated with a form of hemolytic anemia known as hereditary stomatocytosis. However, the function of stomatin is not fully understood. An open reading frame, PH1511, from the hyperthermophilic archaeon Pyrococcus horikoshii encodes p-stomatin, a prokaryotic stomatin. Here, we report the first crystal structure of a stomatin ortholog, the core domain of the p-stomatin PH1511p (residues 56-234 of PH1511p, designated as PhSto(CD)). PhSto(CD) forms a novel homotrimeric structure. Three alpha/beta domains form a triangle of about 50 A on each side, and three alpha-helical segments of about 60 A in length extend from the apexes of the triangle. The alpha/beta domain of PhSto(CD) is partly similar in structure to the band-7 domain of mouse flotillin-2. While the alpha/beta domain is relatively rigid, the alpha-helical segment shows conformational flexibility, adapting to the neighboring environment. One alpha-helical segment forms an anti-parallel coiled coil with another alpha-helical segment from a symmetry-related molecule. The alpha-helical segment shows a heptad repeat pattern, and mainly hydrophobic residues form a coiled-coil interface. According to chemical cross-linking experiments, PhSto(CD) would be able to assemble into an oligomeric form. The coiled-coil fold observed in the crystal probably contributes to self-association.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Archaeal Proteins / chemistry*
  • Crystallography, X-Ray
  • Membrane Proteins / chemistry
  • Mice
  • Models, Molecular
  • Protein Structure, Tertiary
  • Pyrococcus horikoshii / chemistry*
  • Structural Homology, Protein

Substances

  • Archaeal Proteins
  • Membrane Proteins
  • flotillins

Associated data

  • PDB/3BK6