Specific roles of protein-phospholipid interactions in the yeast cytochrome bc1 complex structure.
Biochemical data have shown that specific, tightly bound phospholipids are essential for activity of the cytochrome bc1 complex (QCR), an integral membrane protein of the respiratory chain. However, the structure and function of such phospholipids are not yet known. Here we describe five phospholipid molecules and one detergent molecule in the X-ray structure of yeast QCR at 2.3 A resolution. Their individual binding sites suggest specific roles in facilitating structural and functional integrity of the enzyme. Interestingly, a phosphatidylinositol molecule is bound in an unusual interhelical position near the flexible linker region of the Rieske iron-sulfur protein. Two possible proton uptake pathways at the ubiquinone reduction site have been identified: the E/R and the CL/K pathway. Remarkably, cardiolipin is positioned at the entrance to the latter. We propose that cardiolipin ensures structural integrity of the proton-conducting protein environment and takes part directly in proton uptake. Site-directed mutagenesis of ligating residues confirmed the importance of the phosphatidylinositol- and cardiolipin-binding sites.
Lange
C
C
Max-Planck-Institut für Biophysik, Heinrich-Hoffmann-Strasse 7, D-60528 Frankfurt, Germany.
Nett
J H
JH
Trumpower
B L
BL
Hunte
C
C
D001665:Binding Sites; D015153:Blotting, Western; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003902:Detergents / Q000494:pharmacology; D004579:Electron Transport; D014450:Electron Transport Complex III / Q000737:chemistry* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010716:Phosphatidylinositols / Q000737:chemistry; D010743:Phospholipids / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011522:Protons; D011809:Quinones / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D014451:Ubiquinone / Q000378:metabolism
D002308:Cardiolipins; D003902:Detergents; D008055:Lipids; D010716:Phosphatidylinositols; D010743:Phospholipids; D011522:Protons; D011809:Quinones; D014451:Ubiquinone; D014450:Electron Transport Complex III