Protein Family Models

The DisA protein is a bacterial checkpoint protein that dimerises into an octameric complex. The protein consists of three distinct domains. the first, N-terminal region, from 1-145 is globular and is represented by family DisA_N, Pfam:PF02457; the next 146-289 residues is this domain that consists of an elongated bundle of three alpha helices (alpha-6, alpha-10, and alpha-11), one side of which carries an additional three helices (alpha7-9), thus forming a spine like-linker between domains 1 and 3. The C-terminal residues of domain 3 are family HHH, Pfam:PF00633, the specific DNA-binding domain. The octameric complex thus has structurally linked nucleotide-binding and DNA-binding HhH domains and the nucleotide-binding domains are bound to a cyclic di-adenosine phosphate such that DisA is a specific di-adenylate cyclase. The di-adenylate cyclase activity is strongly suppressed by binding to branched DNA, but not to duplex or single-stranded DNA, suggesting a role for DisA as a monitor of the presence of stalled replication forks or recombination intermediates via DNA structure-modulated c-di-AMP synthesis [1]. [1]. 18439896. Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination intermediates. Witte G, Hartung S, Buttner K, Hopfner KP;. Mol Cell. 2008;30:167-178. (from Pfam)

Date:

2024-10-16

The DisA protein is a bacterial checkpoint protein that dimerises into an octameric complex. The protein consists of three distinct domains. This domain is the first and is a globular, nucleotide-binding region; the next 146-289 residues constitute the DisA-linker family, Pfam:PF10635, that consists of an elongated bundle of three alpha helices (alpha-6, alpha-10, and alpha-11), one side of which carries an additional three helices (alpha7-9), which thus forms a spine like-linker between domains 1 and 3. The C-terminal residues, of domain 3, are represented by family HHH, Pfam:PF00633, the specific DNA-binding domain. The octameric complex thus has structurally linked nucleotide-binding and DNA-binding HhH domains and the nucleotide-binding domains are bound to a cyclic di-adenosine phosphate such that DisA is a specific di-adenylate cyclase. This N-terminal domain has been identified as a diadenylate cyclase (DAC) responsible for producing c-di-AMP from two molecules of ATP [1]. The di-adenylate cyclase activity is strongly suppressed by binding to branched DNA, but not to duplex or single-stranded DNA, suggesting a role for DisA as a monitor of the presence of stalled replication forks or recombination intermediates via DNA structure-modulated c-di-AMP synthesis [2]. [1]. 32095817. Cyclic di-AMP, a second messenger of primary importance: tertiary structures and binding mechanisms. He J, Yin W, Galperin MY, Chou SH;. Nucleic Acids Res. 2020 Feb 25. pii: 5755; [Epub ahead of print]. [2]. 18439896. Structural biochemistry of a bacterial checkpoint protein reveals diadenylate cyclase activity regulated by DNA recombination . TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-16

DNA integrity scanning protein DisA participates in a DNA-damage check-point and is active prior to asymmetric division when DNA is damaged; has diadenylate cyclase activity, catalyzing the condensation of two ATP molecules into cyclic di-AMP, which acts as a signaling molecule that couples DNA integrity with progression of sporulation

Date:

2018-08-28

Non-specific DNA-binding; scans chromosomes during sporulation for DNA-damage; delays initiation of sporulation; participates in a checkpoint signaling cascade for cell-cycle progression and DNA repair

Gene:

disA

Date:

2021-02-03