Cytochrome c impaled: investigation of the extended lipid anchorage of a soluble protein to mitochondrial membrane models.
Cyt c (cytochrome c) has been traditionally envisioned as rapidly diffusing in two dimensions at the surface of the mitochondrial inner membrane when not engaged in redox reactions with physiological partners. However, the discovery of the extended lipid anchorage (insertion of an acyl chain of a bilayer phospholipid into the protein interior) suggests that this may not be exclusively the case. The physical and structural factors underlying the conformational changes that occur upon interaction of ferrous cyt c with phospholipid membrane models have been investigated by monitoring the extent of the spin state change that result from this interaction. Once transiently linked by electrostatic forces between basic side chains and phosphate groups, the acyl chain entry may occur between two parallel hydrophobic polypeptide stretches that are surrounded by positively charged residues. Alteration of these charges, as in the case of non-trimethylated (TML72K) yeast cyt c and Arg91Nle horse cyt c (where Nle is norleucine), led to a decline in the binding affinity for the phospholipid liposomes. The electrostatic association was sensitive to ionic strength, polyanions and pH, whereas the hydrophobic interactions were enhanced by conformational changes that contributed to the loosening of the tertiary structure of cyt c. In addition to proposing a mechanistic model for the extended lipid anchorage of cyt c, we consider what, if any, might be the physiological relevance of the phenomenon.
Kalanxhi
Erta
E
Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada B3H1X5.
Wallace
Carmichael J A
CJ
D000818:Animals; D045304:Cytochromes c / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012995:Solubility; D055672:Static Electricity; D015003:Yeasts
D008565:Membrane Proteins; D010743:Phospholipids; D045304:Cytochromes c