5BQX: Crystal Structure Of Human Sting In Complex With 3'2'-cgamp

Cyclic GMP-AMP containing a unique combination of mixed phosphodiester linkages (2'3'-cGAMP) is an endogenous second messenger molecule that activates the type-I IFN pathway upon binding to the homodimer of the adaptor protein STING on the surface of endoplasmic reticulum membrane. However, the preferential binding of the asymmetric ligand 2'3'-cGAMP to the symmetric dimer of STING represents a physicochemical enigma. Here we show that 2'3'-cGAMP, but not its linkage isomers, adopts an organized free-ligand conformation that resembles the STING-bound conformation and pays low entropy and enthalpy costs in converting into the active conformation. Our results demonstrate that analyses of free-ligand conformations can be as important as analyses of protein conformations in understanding protein-ligand interactions.
PDB ID: 5BQXDownload
MMDB ID: 130381
PDB Deposition Date: 2015/5/29
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 5BQX: dimeric; determined by author and by software (PISA)
Molecular Components in 5BQX
Label Count Molecule
Proteins (2 molecules)
Stimulator of Interferon Genes Protein(Gene symbol: TMEM173)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

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