Publication Abstract from PubMed
Cyclic di-guanosine monophosphate (c-di-GMP) is a ubiquitous bacterial second messenger that controls the switch from a single-cell lifestyle to surface-attached, multicellular communities called biofilms. PilZ domain proteins are a family of bacterial c-di-GMP receptors, which control various cellular processes. We have solved the solution structure of the Pseudomonas aeruginosa single-domain PilZ protein PA4608 in complex with c-di-GMP by NMR spectroscopy. Isotope labeling by 13C and 15N of both the ligand and the protein made it possible to define the structure of c-di-GMP in the complex at high precision by a large number of intermolecular and intraligand NOEs and by two intermolecular hydrogen bond scalar couplings. Complex formation induces significant rearrangements of the C- and N-terminal parts of PA4608. C-di-GMP binds as an intercalated, symmetric dimer to one side of the beta-barrel thereby displacing the C-terminal helix of the apo state. The N-terminal RxxxR PilZ domain motif, which is flexible in the apo state, wraps around the ligand and in turn ties the displaced C-terminus in a loose manner by a number of hydrophic contacts. The recognition of the dimeric ligand is achieved by numerous H-bonds and stacking interactions involving residues R8, R9, R10, R13 of the PilZ motif, as well as beta-barrel residues D35 and W77. As a result of the rearrangement of the N- and C-termini, a highly negative surface is created on one side of the protein complex. We propose that the movement of the termini and the resulting negative surface forms the basis for downstream signaling.
Solution structure of the PilZ domain protein PA4608 complex with c-di-GMP identifies charge clustering as molecular readout.,Habazettl J, Allan MG, Jenal U, Grzesiek S J Biol Chem. 2011 Feb 10. PMID:21310957[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
