2L74

Solution structure of the PilZ domain protein PA4608 complex with c-di-GMP identifies charge clustering as molecular readout

Summary for 2L74

• Entry DOI: 10.2210/pdb2l74/pdb
• Related: 1YWU 3KYF
• Descriptor: Putative uncharacterized protein PA4608, 9,9'-[(2R,3R,3aS,5S,7aR,9R,10R,10aS,12S,14aR)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecine-2,9-diyl]bis(2-amino-1,9-dihydro-6H-purin-6-one) (2 entities in total)
• Functional Keywords: pilz, pa4608, c-di-gmp, unknown function, c-di-gmp binding protein
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 1
• Total formula weight: 18145.57

Authors

Habazettl, J.,Allan, M.,Jenal, U.,Grzesiek, S. (deposition date: 2010-12-02, release date: 2011-02-09, Last modification date: 2024-05-01)

Primary citation

Habazettl, J.,Allan, M.G.,Jenal, U.,Grzesiek, S.
Solution structure of the PilZ domain protein PA4608 complex with cyclic di-GMP identifies charge clustering as molecular readout
J.Biol.Chem., 286:14304-14314, 2011

PubMed Abstract: Cyclic diguanosine 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 (13)C and (15)N 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 β-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 hydrophobic contacts. The recognition of the dimeric ligand is achieved by numerous H-bonds and stacking interactions involving residues Arg(8), Arg(9), Arg(10), and Arg(13) of the PilZ motif, as well as β-barrel residues Asp(35) and Trp(77). 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 form the basis for downstream signaling.

PubMed: 21310957
DOI: 10.1074/jbc.M110.209007

Experimental method

SOLUTION NMR