Structural and kinetic studies of imidazole binding to two members of the cytochrome c6 family reveal an important role for a conserved heme pocket residue
Badri S. Rajagopal, Michael T. Wilson, Derek S. Bendall, Christopher J. Howe and Jonathan A.R. Worrall[1]
Molecular Tour
is a member of the class I family of c-type cytochromes with a distinctive and a . They function in the photosynthetic electron transport chain of cyanobacteria where they shuttle an electron from the cytochrome b6f complex to photosystem I. Structures of numerous cytochrome c6 proteins have been determined and all have the . In the present work we have solved the structure of the Q51V site-directed variant of Phormidium laminosum cytochrome c6. This project is part of a study that is aimed at gaining insight into protein factors which modulate the heme mid-point redox potential in the cytochrome c6 family. The Q51V variant has been shown to tune over 100 mV of heme redox potential, which for a single heme pocket mutation is very significant and has consequences for function.
The Q51V structure confirms that the has the same side-chain orientation in the heme pocket as found in other cytochrome c6 proteins, that naturally have a Val at this position. The significance of this structure is that the and an . Two other structures of imidazole cyt c-adducts have been reported, but neither appear to undergo the . Both protein and heme structural changes are observed, with the later centered on a accompanied by the and the .
Protein (un)folding studies on cytochrome c have revealed that (un)folding involves structural units called 'foldons'. The regions in the Q51V imidazole-adduct where structural changes occur map well to the two foldons predicted to unfold first in cytochrome c. Thus , leading to the formation of an early unfolding intermediate that is stabilised by , enabling it to be captured in the crystalline form.
PDB reference: Structure of the imidazole-adduct of the Phormidium laminosum cytochrome c6 Q51V variant, 3ph2.
