title: Structural characterization reveals that a PilZ domain protein undergoes substantial conformational change upon binding to cyclic dimeric guanosine monophosphate.
abstract: PA4608 is a single PilZ domain protein from Pseudomonas aeruginosa that binds to cyclic dimeric guanosine monophosphate (c-di-GMP). Although the monomeric structure of unbound PA4608 has been studied in detail, the molecular details of c-di-GMP binding to this protein are still uncharacterized. Hence, we determined the solution structure of c-di-GMP bound PA4608. We found that PA4608 undergoes conformational changes to expose the c-di-GMP binding site by ejection of the C-terminal 3(10) helix. A dislocation of the C-terminal tail in the presence of c-di-GMP implies that this region acts as a lid that alternately covers and exposes the hydrophobic surface of the binding site. In addition, mutagenesis and NOE data for PA4608 revealed that conserved residues are in contact with the c-di-GMP molecule. The unique structural characteristics of PA4608, including its monomeric state and its ligand binding characteristics, yield insight into its function as a c-di-GMP receptor.
authors.affiliation: Department of Chemistry, KAIST, 373-1 Guseong-dong, Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Jae-Sun
authors.initials: JS
authors.lastname: Shin
authors.forename: Kyoung-Seok
authors.initials: KS
authors.lastname: Ryu
authors.forename: Junsang
authors.initials: J
authors.lastname: Ko
authors.forename: Arum
authors.initials: A
authors.lastname: Lee
authors.forename: Byong-Seok
authors.initials: BS
authors.lastname: Choi
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; C097615:PilZ protein, Pseudomonas aeruginosa; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP