TorD Family Proteins
The ‘TorD Family’ of peptide binding-proteins is vast and includes a number of proteins for which 3-D crystal structures have been determined. All but one of these structures emerged from ‘structural genomics’ initiatives somewhere around the world. The TorD protein from Shewanella massilia (PDB number 1n1c) crystallized as a domain-swapped homodimer (Tranier et al. 2003 Structure 11:165). True TorD proteins, such as this one, are involved in the biosynthesis of trimethylamine N-oxide (TMAO) reductases and bind tightly to the apoprotein at several different positions (most notably the signal peptide). The physiological role of the homodimerization of this protein remains unknown, all other structures for TorD family proteins are (probably) monomeric.
The domain-swapped TorD homodimer
The NarJ protein from Archaeoglobus fulgidus (PDB number 2o9x) is a monomeric protein involved in the biosynthesis of a nitrate reductase (Kirillova et al. 2007 Acta Crystallogr Sect D 63:348). A second member of the TorD family from A. fulgigus, Af0160 (PDB number 2idg), has been crystallized and the structure solved. This protein was solved as a trimer, but it is not yet clear whether this is physiologically relevant or related to the Sh. massilia TorD dimeric structure.
NarJ monomer
Af0160 as a homotrimer
The DmsD protein from Salmonella enterica serovar Typhimurium (PDB number 1s9u) is a monomeric protein involved in the biosynthesis of a dimethyl sulphoxide (DMSO) reductase (Qui et al. 2008. Proteins 71:523). Like TorD, this protein binds to the signal peptide of the DMSO reductase.
The Salmonella DmsD protein
All of these TorD family proteins are similar but different. The overall folds are similar and they share conserved amino acids – however they have exquisite selectivity in peptide binding. One main aim of the group is to understand, and harness, the molecular basis of this binding specificity.
NapD Family Proteins
The napD gene has been known for many years since it is always genetically-linked to the napA gene, which encodes the periplasmic nitrate reductase. NapA-like nitrate reductases have been studied in great depth all over the world because of the central place of this enzyme in the global nitrogen cycle. It was also known for some time that the napD gene was “something to do with NapA biosynthesis”, though the details of exactly what were missing. It came as a surprise, therefore, when NapD turned out to be a signal peptide binding protein (Maillard et al. 2007 PNAS 104: 15641), since we had been fixated on the TorD family being the paradigm examples of such proteins. E. coli NapD has a completely different structure to TorD-like proteins. The high resolution NMR solution structure reveals a ferredoxin-like fold (PDB number 2jsx), which is very common and employed in ligand binding sites for a broad spectrum of biological processes.
NapD has a ferredoxin-like fold and a flexible C-terminus
Another aim of the group, therefore, is to compare and contrast the structure and function of the NapD family with the TorD family of biosynthetic chaperones.
Hydrogen Metabolism and Hydrogenase Biosynthesis
Under Construction...