Surf1, associated with Leigh syndrome in humans, is a heme-binding protein in bacterial oxidase biogenesis.

Abstract

Biogenesis of mitochondrial cytochrome c oxidase (COX) relies on a large number of assembly factors, among them the transmembrane protein Surf1. The loss of human Surf1 function is associated with Leigh syndrome, a fatal neurodegenerative disorder caused by severe COX deficiency. In the bacterium Paracoccus denitrificans, two homologous proteins, Surf1c and Surf1q, were identified, which we characterize in the present study. When coexpressed in Escherichia coli together with enzymes for heme a synthesis, the bacterial Surf1 proteins bind heme a in vivo. Using redox difference spectroscopy and isothermal titration calorimetry, the binding of the heme cofactor to purified apo-Surf1c and apo-Surf1q is quantified: Each of the Paracoccus proteins binds heme a in a 1:1 stoichiometry and with Kd values in the submicromolar range. In addition, we identify a conserved histidine as a residue crucial for heme binding. Contrary to most earlier concepts, these data support a direct role of Surf1 in heme a cofactor insertion into COX subunit I by providing a protein-bound heme a pool.

• Authors: Freya A Bundschuh, Achim Hannappel, Oliver Anderka, Bernd Ludwig
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 284 Issue 38 Pg. 25735-41 (Sep 18 2009) ISSN: 1083-351X [Electronic] United States
• PMID: 19625251 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Membrane Proteins
• Mitochondrial Proteins
• Surf-1 protein
• Heme
• Electron Transport Complex IV

Topics

• Bacterial Proteins (biosynthesis, chemistry)
• Electron Transport Complex IV (biosynthesis, chemistry)
• Heme (chemistry, metabolism)
• Humans
• Leigh Disease (genetics, metabolism)
• Membrane Proteins (chemistry, genetics, metabolism)
• Mitochondrial Proteins (chemistry, genetics, metabolism)
• Paracoccus denitrificans (enzymology, genetics)
• Protein Binding (genetics)