Nitrobindin: An ubiquitous family of all β-barrel heme-proteins

Abstract

Rhodnius prolixus nitrophorins (Rp-NPs), Arabidopsis thaliana nitrobindin (At-Nb), and Homo sapiens THAP4 (Hs-THAP4) are the unique known proteins that use a β-barrel fold to bind ferric heme, which is devoted to NO transport and/or catalysis. The eight-stranded antiparallel β-barrel Rp-NPs, which represent the only heme-binding lipocalins, are devoted to deliver NO into the blood vessel of the host and to scavenge histamine during blood sucking. Regarding Nbs, crystallographic data suggest the ability of At-Nb and Hs-THAP4 to bind ferric heme; however, no data are available with respect to these functions in the natural host. Here, a bioinformatics investigation based on the amino acid sequences and three-dimensional structures of At-Nb and Hs-THAP4 suggests a conservation of the 10-stranded antiparallel β-barrel Nb structural module in all life kingdoms of the evolutionary ladder. In particular, amino acid residues involved in the heme recognition and in the structure stabilization of the Nb structural module are highly conserved (identity > 29%; homology > 83%). Moreover, molecular models of putative Nbs from different organisms match very well with each other and known three-dimensional structures of Nbs. Furthermore, phylogenetic tree reconstruction indicates that NPs and Nbs group in distinct clades. These data indicate that 10-stranded β-barrel Nbs constitute a new ubiquitous heme protein family spanning from bacteria to Homo sapiens.