2',3'-cyclic GMP-AMP binding

Definition

Target type: molecularfunction

Binding to 2',3' cyclic GMP-AMP (cGAMP) nucleotide, a cyclic purine dinucleotide that consists of AMP and GMP units cyclized via 2',5' and 3',5' linkages. [GOC:dph, PMID:23258412, PMID:23910378]

2',3'-cyclic GMP-AMP (cGAMP) is a cyclic dinucleotide second messenger that plays a critical role in innate immune signaling. It is synthesized by the enzyme cGAS upon recognition of cytosolic DNA from viruses or bacteria. cGAMP functions as an activator of the STING protein, a key signaling molecule in the innate immune response.

The molecular function of cGAMP binding to STING involves several key steps:

1. **Binding to the STING dimer:** cGAMP binds to the dimeric STING protein through two distinct sites. One site is located in the transmembrane domain, while the other is located in the cytosolic domain. This binding event initiates conformational changes within the STING protein.
2. **Induction of STING oligomerization:** Upon binding to cGAMP, STING molecules undergo oligomerization, forming higher-order structures. This oligomerization is essential for activating downstream signaling pathways.
3. **Recruitment of TBK1:** The oligomerized STING complex recruits the protein kinase TBK1. TBK1 is a key player in the activation of the interferon regulatory factor 3 (IRF3) pathway.
4. **Activation of IRF3:** TBK1 phosphorylates and activates IRF3, a transcription factor responsible for the expression of type I interferons (IFNs).

The binding of cGAMP to STING triggers a cascade of events that ultimately lead to the production of type I IFNs, which are essential for the antiviral and antibacterial immune responses. The specific molecular interactions between cGAMP and STING, including the precise conformational changes and the roles of different amino acid residues, are being actively studied to gain a deeper understanding of this critical signaling pathway.
'"

Proteins (2)

Compounds (10)