4RLE

Crystal structure of the c-di-AMP binding PII-like protein DarA

Summary for 4RLE

• Entry DOI: 10.2210/pdb4rle/pdb
• Descriptor: Uncharacterized protein YaaQ, (2R,3R,3aS,5R,7aR,9R,10R,10aS,12R,14aR)-2,9-bis(6-amino-9H-purin-9-yl)octahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8 ]tetraoxadiphosphacyclododecine-3,5,10,12-tetrol 5,12-dioxide, NICKEL (II) ION, ... (4 entities in total)
• Functional Keywords: pii-like, cdiamp, unknown function
• Biological source: Bacillus subtilis
• Total number of polymer chains: 1
• Total formula weight: 13669.85

Authors

Dickmanns, A.,Neumann, P.,Ficner, R. (deposition date: 2014-10-16, release date: 2014-12-03, Last modification date: 2023-09-20)

Primary citation

Gundlach, J.,Dickmanns, A.,Schroder-Tittmann, K.,Neumann, P.,Kaesler, J.,Kampf, J.,Herzberg, C.,Hammer, E.,Schwede, F.,Kaever, V.,Tittmann, K.,Stulke, J.,Ficner, R.
Identification, Characterization, and Structure Analysis of the Cyclic di-AMP-binding PII-like Signal Transduction Protein DarA.
J.Biol.Chem., 290:3069-3080, 2015

PubMed Abstract: The cyclic dimeric AMP nucleotide c-di-AMP is an essential second messenger in Bacillus subtilis. We have identified the protein DarA as one of the prominent c-di-AMP receptors in B. subtilis. Crystal structure analysis shows that DarA is highly homologous to PII signal transducer proteins. In contrast to PII proteins, the functionally important B- and T-loops are swapped with respect to their size. DarA is a homotrimer that binds three molecules of c-di-AMP, each in a pocket located between two subunits. We demonstrate that DarA is capable to bind c-di-AMP and with lower affinity cyclic GMP-AMP (3'3'-cGAMP) but not c-di-GMP or 2'3'-cGAMP. Consistently the crystal structure shows that within the ligand-binding pocket only one adenine is highly specifically recognized, whereas the pocket for the other adenine appears to be promiscuous. Comparison with a homologous ligand-free DarA structure reveals that c-di-AMP binding is accompanied by conformational changes of both the fold and the position of the B-loop in DarA.

PubMed: 25433025
DOI: 10.1074/jbc.M114.619619

Experimental method

X-RAY DIFFRACTION (1.3 Å)