Life (26) MrpA MrpD NuoL NuoM and NuoN. Plus nt-Nha.

A few years ago I mentioned this paper

Homologous protein subunits from Escherichia coli NADH:quinone oxidoreductase can functionally replace MrpA and MrpD in Bacillus subtilis

In brief they had Bacillus subtilis strains with either an MrpA knockout or an MrpD knockout. The E coli complex I equivalent of NuoL can replace MrpA and the NuoN equivalent can replace MrpD in B subtilis. NouM doesn't seem do either. But all five subunits look very similar to each other and all are clearly related. NuoL, NuoM and NuoN are always described as "antiporter-like". MrpA and MrpD are thought to be antiporters but none ever work alone, the whole complex is needed, so they are probably "antiporter-like" too. They all appear to have been derived from an antiporter but any intrinsic antiporting has been lost.


Which makes me sad because it seems very probable that all of the above subunits are derived from the primordial antiporter at the origin of life which initiated Na+ bioenergetics and all that followed on from that.

Then came Natranaerobius thermophilus. N thermophilus is not really in the league of P furiosus, it's okay growing at up to 57 degC (which will still scald you) but no higher and it has adapted its membrane to remain proton tight at this temperature. BTW it's strictly anaerobic, is an halophile and an alkaliphile. It has (among several) one family of modern antiporters which are clearly genetically related to the MrpA of modern Clostridium tetani (and probably all other MrpAs). Modern nt-Nha is a fully functional antiporter as a stand-alone single gene protein. As these folks say:

The halophilic alkalithermophile Natranaerobius thermophilus adapts to multiple environmental extremes using a large repertoire of Na+(K+)/H+ antiporters

"Gene nt-Nha had 35% identity to the shaA (mrPA) gene of Clostridium tetani. The Mrp proteins belong to the monovalent cation/proton antiporter-3 protein family. This family is composed of multi-component Na+/H+ and K+/H+ antiporters encoded by operons of six or seven genes, and all genes are required for full function in Na+ and alkali resistance (Ito et al., 2000). Sequence analysis of the
regions surrounding gene nt-Nha, however, did not show that it was part of an operon. This indicates that gene nt-Nha does not encode a subunit of an Mrp system, but rather a mono-subunit antiporter".

EDIT number 2: These people have isolated an MrpA from an archaeal species which will antiport on its own, which makes it very similar to nt-Nha. There is also some evidence that complex I can function as a partial Na+/H+ antiporter as in this paper. NuoL is the main suspect. END EDIT.

Neither the MrpA-like nt-Nha nor the modern MrpA subunit of C tetani is in any way primordial. Both are used to extrude Na+ in exchange for H+ but this is not to drive Na+ energetics, they are much more associated with resistance to high Na+ concentrations and to alkaline pH environments. So it is possible that the N Thermophilus nt-Nha is a relatively modern derivative (it does use a proton tight membrane) of a relatively modern MrpA.

Or, more excitingly, it's possible that an ancestral Na+/H+ antiporter gave rise to both nt-Nha and MrpA. This would be the interesting option as it is possible that the Na+ binding sites, the route across the antiporter for Na+ and the mechanism for activation might just give us the technique used by the original ancestral antiporter. Genetics and structure-function modeling look to be the way to go but I can't see that it's been done yet.

Edit: Found the structure homology studies in here, lying around on my hard drive for years too. End edit.

Peter