Novel heme-based oxygen sensor with a revealing evolutionary history.

To monitor fluctuations in oxygen concentration, cells use sensory proteins often containing heme cofactors. Here, we identify a new class of heme-binding oxygen sensors, reveal their unusual phylogenetic origin, and propose a sensing mode of a member of this class. We show that heme is bound noncovalently to the central region of AppA, an oxygen and light sensor from Rhodobacter sphaeroides. The addition of oxygen to ferrous AppA discoordinated the heme, and subsequent oxygen removal fully restored the heme coordination. In vitro, the extent of heme discoordination increased gradually with the rise in oxygen levels over a broad concentration range. This response correlated well with the gradual decrease in transcription of photosynthesis genes regulated by AppA and its partner repressor PpsR. We conclude that the AppA-PpsR regulatory system functions as an oxygen-dependent transcriptional rheostat. We identified a new domain embedded in the central region of AppA and designated it SCHIC for sensor containing heme instead of cobalamin. A phylogenetic analysis revealed that SCHIC domain proteins form a distinct cluster within a superfamily that includes vitamin B(12)-binding proteins and other proteins that may bind other kinds of tetrapyrroles.