4RT0

Structure of the Alg44 PilZ domain from Pseudomonas aeruginosa PAO1 in complex with c-di-GMP

4RT0 の概要

• エントリーDOI: 10.2210/pdb4rt0/pdb
• 関連するPDBエントリー: 4RT1
• 分子名称: Alginate biosynthesis protein Alg44, 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), 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: pilz domain, c-di-gmp receptor, protein binding
• 由来する生物種: Pseudomonas aeruginosa
• 細胞内の位置: Periplasm : Q9HY69
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 41724.83

構造登録者

Whitfield, G.B.,Whitney, J.C. (登録日: 2014-11-12, 公開日: 2015-04-08, 最終更新日: 2024-11-06)

主引用文献

Whitney, J.C.,Whitfield, G.B.,Marmont, L.S.,Yip, P.,Neculai, A.M.,Lobsanov, Y.D.,Robinson, H.,Ohman, D.E.,Howell, P.L.
Dimeric c-di-GMP Is Required for Post-translational Regulation of Alginate Production in Pseudomonas aeruginosa.
J.Biol.Chem., 290:12451-12462, 2015

PubMed Abstract: Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZ domain fold with a dimerization mode not previously observed for this family of proteins. Calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. These results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa.

PubMed: 25817996
DOI: 10.1074/jbc.M115.645051

実験手法

X-RAY DIFFRACTION (1.8 Å)