4F8L: X-ray structure of PsaA from Yersinia pestis, in complex with galactose and AEBSF

The pH 6 antigen (Psa) of Yersinia pestis consists of fimbriae that bind to two receptors: beta1-linked galactosyl residues in glycosphingolipids and the phosphocholine group in phospholipids. Despite the ubiquitous presence of either moiety on the surface of many mammalian cells, Y. pestis appears to prefer interacting with certain types of human cells, such as macrophages and alveolar epithelial cells of the lung. The molecular mechanism of this apparent selectivity is not clear. Site-directed mutagenesis of the consensus choline-binding motif in the sequence of PsaA, the subunit of the Psa fimbrial homopolymer, identified residues that abolish galactosylceramide binding, phosphatidylcholine binding, or both. The crystal structure of PsaA in complex with both galactose and phosphocholine reveals separate receptor binding sites that share a common structural motif, thus suggesting a potential interaction between the two sites. Mutagenesis of this shared structural motif identified Tyr126, which is part of the choline-binding consensus sequence but is found in direct contact with the galactose in the structure of PsaA, important for both receptor binding. Thus, this structure depicts a fimbrial subunit that forms a polymeric adhesin with a unique arrangement of dual receptor binding sites. These findings move the field forward by providing insights into unique types of multiple receptor-ligand interactions and should steer research into the synthesis of dual receptor inhibitor molecules to slow down the rapid progression of plague.
PDB ID: 4F8LDownload
MMDB ID: 110253
PDB Deposition Date: 2012/5/17
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.5  Å
Source Organism:
Similar Structures:
Biological Unit for 4F8L: monomeric; determined by author and by software (PISA)
Molecular Components in 4F8L
Label Count Molecule
Protein (1 molecule)
PH 6 Antigen(Gene symbol: psaA)
Molecule annotation
Chemicals (41 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB