PilZ domain

PA4608 is a 125 residue protein from Pseudomonas aeruginosa with a recent identification as a PilZ domain and putative bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) adaptor protein that plays a role in bacterial second-messenger regulated processes. The nuclear magnetic resonance (NMR) structure of PA4608 has been determined and c-di-GMP binding has been confirmed by NMR titration studies. The monomeric core structure of PA4608 contains a six-stranded anti-parallel beta barrel flanked by three helices. Conserved surface residues among PA4608 homologs suggest the c-di-GMP binding site is at one end of the barrel and includes residues in the helices as well as in the unstructured N-terminus. Chemical shift changes in PA4608 resonances upon titration with c-di-GMP confirm binding. This evidence supports the hypothesis that proteins containing PilZ domains are the long-sought c-di-GMP adaptor proteins.

NMR structure and binding studies confirm that PA4608 from Pseudomonas aeruginosa is a PilZ domain and a c-di-GMP binding protein., Ramelot TA, Yee A, Cort JR, Semesi A, Arrowsmith CH, Kennedy MA, Proteins. 2007 Feb 1;66(2):266-71. PMID:17096419

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

The second messenger cyclic diguanylate (c-di-GMP) controls the transition between motile and sessile growth in eubacteria, but little is known about the proteins that sense its concentration. Bioinformatics analyses suggested that PilZ domains bind c-di-GMP and allosterically modulate effector pathways. We have determined a 1.9 A crystal structure of c-di-GMP bound to VCA0042/PlzD, a PilZ domain-containing protein from Vibrio cholerae. Either this protein or another specific PilZ domain-containing protein is required for V. cholerae to efficiently infect mice. VCA0042/PlzD comprises a C-terminal PilZ domain plus an N-terminal domain with a similar beta-barrel fold. C-di-GMP contacts seven of the nine strongly conserved residues in the PilZ domain, including three in a seven-residue long N-terminal loop that undergoes a conformational switch as it wraps around c-di-GMP. This switch brings the PilZ domain into close apposition with the N-terminal domain, forming a new allosteric interaction surface that spans these domains and the c-di-GMP at their interface. The very small size of the N-terminal conformational switch is likely to explain the facile evolutionary diversification of the PilZ domain.

The structural basis of cyclic diguanylate signal transduction by PilZ domains., Benach J, Swaminathan SS, Tamayo R, Handelman SK, Folta-Stogniew E, Ramos JE, Forouhar F, Neely H, Seetharaman J, Camilli A, Hunt JF, EMBO J. 2007 Dec 12;26(24):5153-66. Epub 2007 Nov 22. PMID:18034161

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.