Presentation Title

Identification and characterization of a yeast iso-1-cytochrome c C-terminal domain swapped dimer

Presentation Type

Poster Presentation

Area of Focus

Physical and Earth Sciences

Abstract

Domain swapped protein dimers consist of a swapped domain linked by a hinge loop. They have been proposed as a means of achieving larger assemblies potentially contributing to biological cellular activity or conferring disease. Here we present a crystal structure of a C-terminal domain swapped dimer in yeast iso-1-cytochrome c. In this structure the C-terminal alpha helix from one monomer positions itself in the native position of the opposite monomer and vice versa. The highly dynamic heme crevice loop, the most highly conserved portion of the cytochrome c sequence, spans the gap acting as the hinge loop. Interestingly, conversion of the heme crevice loop to the hinge loop results in a loss of the native Met80-heme ligation. This produces an open heme coordination site on each subunit of the dimer. As cytochrome c requires an open heme coordination site to act as a peroxidase, to oxidize cardiolipin and initiate the intrinsic apoptotic pathway, this dimer structure could potentially be a structure particularly suited to function in oxidizing cardiolipin. In fact, a recently reported C-terminal domain swapped dimer of horse cytochrome c demonstrates increased peroxidase activity relative to the monomer. Although the yeast and horse dimer are similar, the hinge loop orientations differ. The hinge loop is two residues longer in the yeast dimer resulting in an increased distance between the heme groups and an altered angle of the hinge loops relative to the horse cytochrome c dimer. Even though they contain similar structure and sequence, the domain swapped yeast iso-1-cytochrome c dimer demonstrates decreased stability compared to the horse cytochrome c dimer.

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Apr 18th, 2:30 PM Apr 18th, 3:50 PM

Identification and characterization of a yeast iso-1-cytochrome c C-terminal domain swapped dimer

UC South Ballroom

Domain swapped protein dimers consist of a swapped domain linked by a hinge loop. They have been proposed as a means of achieving larger assemblies potentially contributing to biological cellular activity or conferring disease. Here we present a crystal structure of a C-terminal domain swapped dimer in yeast iso-1-cytochrome c. In this structure the C-terminal alpha helix from one monomer positions itself in the native position of the opposite monomer and vice versa. The highly dynamic heme crevice loop, the most highly conserved portion of the cytochrome c sequence, spans the gap acting as the hinge loop. Interestingly, conversion of the heme crevice loop to the hinge loop results in a loss of the native Met80-heme ligation. This produces an open heme coordination site on each subunit of the dimer. As cytochrome c requires an open heme coordination site to act as a peroxidase, to oxidize cardiolipin and initiate the intrinsic apoptotic pathway, this dimer structure could potentially be a structure particularly suited to function in oxidizing cardiolipin. In fact, a recently reported C-terminal domain swapped dimer of horse cytochrome c demonstrates increased peroxidase activity relative to the monomer. Although the yeast and horse dimer are similar, the hinge loop orientations differ. The hinge loop is two residues longer in the yeast dimer resulting in an increased distance between the heme groups and an altered angle of the hinge loops relative to the horse cytochrome c dimer. Even though they contain similar structure and sequence, the domain swapped yeast iso-1-cytochrome c dimer demonstrates decreased stability compared to the horse cytochrome c dimer.