Journal:JBIC:7

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.