Structure of the Mg-chelatase cofactor GUN4 reveals a novel hand-shaped fold for porphyrin binding

PLoS Biol. 2005 May;3(5):e151. doi: 10.1371/journal.pbio.0030151. Epub 2005 Apr 26.


In plants, the accumulation of the chlorophyll precursor Mg-protoporphyrin IX (Mg-Proto) in the plastid regulates the expression of a number of nuclear genes with functions related to photosynthesis. Analysis of the plastid-to-nucleus signaling activity of Mg-Proto in Arabidopsis thaliana led to the discovery of GUN4, a novel porphyrin-binding protein that also dramatically enhances the activity of Mg-chelatase, the enzyme that synthesizes Mg-Proto. GUN4 may also play a role in both photoprotection and the cellular shuttling of tetrapyrroles. Here we report a 1.78-A resolution crystal structure of Synechocystis GUN4, in which the porphyrin-binding domain adopts a unique three dimensional fold with a "cupped hand" shape. Biophysical and biochemical analyses revealed the specific site of interaction between GUN4 and Mg-Proto and the energetic determinants for the GUN4.Mg-Proto interaction. Our data support a novel protective function for GUN4 in tetrapyrrole trafficking. The combined structural and energetic analyses presented herein form the physical-chemical basis for understanding GUN4 biological activity, including its role in the stimulation of Mg-chelatase activity, as well as in Mg-Proto retrograde signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arabidopsis / enzymology
  • Arabidopsis / metabolism*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism*
  • Binding Sites
  • Chlorophyll / metabolism
  • Cloning, Molecular
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lyases / metabolism*
  • Porphyrins / metabolism*
  • Protein Folding
  • Recombinant Proteins / metabolism
  • Restriction Mapping


  • Arabidopsis Proteins
  • GUN4 protein, Arabidopsis
  • Intracellular Signaling Peptides and Proteins
  • Porphyrins
  • Recombinant Proteins
  • Chlorophyll
  • Lyases
  • magnesium chelatase

Associated data

  • PDB/1Y6I