3KS0: Crystal Structure Of The Heme Domain Of Flavocytochrome B2 In Complex With Fab B2b4

Citation:
Abstract
Yeast flavocytochrome b(2) (Fcb2) is an L-lactate:cytochrome c oxidoreductase in the mitochondrial intermembrane space participating in cellular respiration. Each enzyme subunit consists of a cytochrome b(5)-like heme domain and a flavodehydrogenase (FDH) domain. In the Fcb2 crystal structure, the heme domain is mobile relative to the tetrameric FDH core in one out of two subunits. The monoclonal antibody B2B4, elicited against the holoenzyme, recognizes only the native heme domain in the holoenzyme. When bound, it suppresses the intramolecular electron transfer from flavin to heme b(2), hence cytochrome c reduction. We report here the crystal structure of the heme domain in complex with the Fab at 2.7 A resolution. The Fab epitope on the heme domain includes the two exposed propionate groups of the heme, which are hidden in the interface between the domains in the complete subunit. The structure discloses an unexpected plasticity of Fcb2 in the neighborhood of the heme cavity, in which the heme has rotated. The epitope overlaps with the docking area of the FDH domain onto the heme domain, indicating that the antibody displaces the heme domain in a movement of large amplitude. We suggest that the binding sites on the heme domain of cytochrome c and of the FDH domain also overlap and therefore that cytochrome c binding also requires the heme domain to move away from the FDH domain, so as to allow electron transfer between the two hemes. Based on this hypothesis, we propose a possible model of the Fcb2.cytochrome c complex. Interestingly, this model shares similarity with that of the cytochrome b(5) x cytochrome c complex, in which cytochrome c binds to the surface around the exposed heme edge of cytochrome b(5). The present results therefore support the idea that the heme domain mobility is an inherent component of the Fcb2 functioning.
PDB ID: 3KS0Download
MMDB ID: 82327
PDB Deposition Date: 2009/11/20
Updated in MMDB: 2010/08
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 3KS0: trimeric; determined by author
Molecular Components in 3KS0
Label Count Molecule
Proteins (3 molecules)
1
Heme Domain of Flavocytochrome B2
Molecule annotation
1
Fragment Antigen Binding B2b4
Molecule annotation
1
Cytochrome B2, Mitochondrial(Gene symbol: CYB2)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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