4rle | pdb_00004rle
Crystal structure of the c-di-AMP binding PII-like protein DarA
Structural highlights
FunctionDARA_BACSU Binds cyclic di-AMP (c-di-AMP) and is probably involved in c-di-AMP-mediated signaling pathways. In vitro, can also bind cyclic GMP-AMP (3'3'-cGAMP), with lower affinity, but not c-di-GMP or 2'3'-cGAMP.[1] Publication Abstract from PubMedThe 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 homo-trimer 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, also 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, while 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. Identification, characterization and structure analysis of the c-di-AMP binding PII-like signal transduction protein DarA.,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 J Biol Chem. 2014 Nov 28. pii: jbc.M114.619619. PMID:25433025[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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