6PWK

Vibrio cholerae LapD S helix-GGDEF-EAL (bound to c-di-GMP)

Summary for 6PWK

• Entry DOI: 10.2210/pdb6pwk/pdb
• Descriptor: GGDEF and EAL domain-containing protein, 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), MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: biofilm formation, cell adhesion, c-di-gmp signaling, receptor, signaling protein
• Biological source: Vibrio cholerae O1 str. 2010EL-1786
• Total number of polymer chains: 2
• Total formula weight: 97460.54

Authors

Giglio, K.M.,Cooley, R.B.,Sondermann, H. (deposition date: 2019-07-23, release date: 2019-10-09, Last modification date: 2023-10-11)

Primary citation

Kitts, G.,Giglio, K.M.,Zamorano-Sanchez, D.,Park, J.H.,Townsley, L.,Cooley, R.B.,Wucher, B.R.,Klose, K.E.,Nadell, C.D.,Yildiz, F.H.,Sondermann, H.
A Conserved Regulatory Circuit Controls Large Adhesins in Vibrio cholerae.
Mbio, 10:-, 2019

PubMed Abstract: The dinucleotide second messenger c-di-GMP has emerged as a central regulator of reversible cell attachment during bacterial biofilm formation. A prominent cell adhesion mechanism first identified in pseudomonads combines two c-di-GMP-mediated processes: transcription of a large adhesin and its cell surface display via posttranslational proteolytic control. Here, we characterize an orthologous c-di-GMP effector system and show that it is operational in , where it regulates two distinct classes of adhesins. Through structural analyses, we reveal a conserved autoinhibition mechanism of the c-di-GMP receptor that controls adhesin proteolysis and present a structure of a c-di-GMP-bound receptor module. We further establish functionality of the periplasmic protease controlled by the receptor against the two adhesins. Finally, transcription and functional assays identify physiological roles of both c-di-GMP-regulated adhesins in surface attachment and biofilm formation. Together, our studies highlight the conservation of a highly efficient signaling effector circuit for the control of cell surface adhesin expression and its versatility by revealing strain-specific variations., the causative agent of the diarrheal disease cholera, benefits from a sessile biofilm lifestyle that enhances survival outside the host but also contributes to host colonization and infectivity. The bacterial second messenger c-di-GMP has been identified as a central regulator of biofilm formation, including in ; however, our understanding of the pathways that contribute to this process is incomplete. Here, we define a conserved signaling system that controls the stability of large adhesion proteins at the cell surface of , which are important for cell attachment and biofilm formation. Insight into the regulatory circuit underlying biofilm formation may inform targeted strategies to interfere with a process that renders this bacterium remarkably adaptable to changing environments.

PubMed: 31796544
DOI: 10.1128/mBio.02822-19

Experimental method

X-RAY DIFFRACTION (2.61 Å)