Featured Article - January 2010
Short description: The discovery of Pleckstrin-homology-like domains in prokaryotes suggests an ancient evolutionary origin for the PH superfamily.
The Pleckstrin homology (PH) domain is common throughout eukaryotes and the PH-like domain is one of the most abundant protein modules in the human genome. Despite its plenitude in eukaryotes, this fold was thought to be absent from bacteria, but a report by Ian Wilson and colleagues in the Journal of Molecular Biology suggests it is abundant in prokaryotes as well.
In eukaryotes, the PH domain is involved in many cellular functions, such as signaling and cytoskeletal organization, and is best known for binding phosphatidylinositol lipids and targeting proteins to the plasma membrane.
The canonical eukaryotic PH domain is a seven-stranded β-sandwich, which forms two anti-parallel, perpendicular β-sheets followed by a carboxy-terminal α-helix. The loops that connect the β-strands vary in length from protein to protein. The overall shape of the bacteria PH-like domain (PHb) reported in this study closely resembles those of eukaryotic PH domains.
PSI JCSG in collaboration with investigators in the PFAM team determined and analyzed the crystal structures of three members of the previously uncharacterized protein family Pfam PF08000, which appears to be involved in the bacterial cell envelope stress response. The proteins were from Shewanella loihica, S. amazonensis and Exiguobacterium sibiricum.
All three structures have at least one domain that is similar to eukaryotic PH-like domains. Two contain a single bacterial PH-like domain (PHb) and the third one an additional helical hairpin attached at the C terminus.
These PHb-containing proteins display rare, higher-order, cyclic symmetry: PHb1 from S. loihica and S. amazonensis have a non-crystallographic C5 symmetry; PHb2 from E. sibiricum has C12 symmetry. Wilson and colleagues hypothesize that these proteins could belong to membrane-bound transporters or pores and that the PHb domain facilitates oligomerization.
This is the first evidence for the existence of PH-like domains in bacteria, and searches for proteins with similar structures suggest that several other uncharacterized proteins families are likely to contain PHb domains. Thus, the PH domain superfamily probably existed before prokaryotes and eukaryotes diverged.
Q. Xu, A. Bateman, R. D. Finn, P. Abdubek, T. Astakhova et al. Bacterial Pleckstrin homology domains: A prokaryotic origin for the PH domain.
J. Mol. Biol. (2009). doi:10.1016/j.jmb.2009.11.006