Structural analysis of the human Golgi-associated plant pathogenesis related protein GAPR-1 implicates dimerization as a regulatory mechanism

J Mol Biol. 2004 May 21;339(1):173-83. doi: 10.1016/j.jmb.2004.03.015.

Abstract

The plant pathogenesis related proteins group 1 (PR-1) and a variety of related mammalian proteins constitute a PR-1 protein family that share sequence and structural similarities. GAPR-1 is a unique family member as thus far it is the only PR-1 family member that is not co-translationally targeted to the lumen of the endoplasmic reticulum before trafficking to either vacuoles or secretion. Here we report that GAPR-1 may form dimers in vitro and in vivo, as determined by yeast two-hybrid screening, biochemical and biophysical assays. The 1.55A crystal structure demonstrates that GAPR-1 is structurally homologous to the other PR-1 family members previously solved (p14a and Ves V 5). Through an examination of inter-molecular interactions between GAPR-1 molecules in the crystal lattice, we propose a number of the highly conserved amino acid residues of the PR-1 family to be involved in the regulation of dimer formation of GAPR-1 with potential implications for other PR-1 family members. We show that mutagenesis of these conserved amino acid residues leads to a greatly increased dimer population. A recent report suggests that PR-1 family members may exhibit serine protease activity and further examination of the dimer interface of GAPR-1 indicates that a catalytic triad similar to that of serine proteases may be formed across the dimer interface by residues from both molecules within the dimer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Cricetinae
  • Crystallization
  • Crystallography, X-Ray
  • Dimerization
  • Golgi Apparatus / chemistry*
  • Golgi Apparatus / metabolism*
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques

Substances

  • GLIPR2 protein, human
  • Membrane Proteins

Associated data

  • PDB/1SMB