Summary for 4KC0
| Entry DOI | 10.2210/pdb4kc0/pdb |
| Related | 4KBY |
| Descriptor | Stimulator of interferon genes protein (2 entities in total) |
| Functional Keywords | mouse sting, immune system |
| Biological source | Mus musculus (mouse) |
| Cellular location | Endoplasmic reticulum membrane; Multi-pass membrane protein: Q3TBT3 |
| Total number of polymer chains | 2 |
| Total formula weight | 47181.69 |
| Authors | Chin, K.H.,Su, Y.C.,Tu, J.L.,Chou, S.H. (deposition date: 2013-04-24, release date: 2013-05-29, Last modification date: 2024-03-20) |
| Primary citation | Chin, K.H.,Tu, Z.L.,Su, Y.C.,Yu, Y.J.,Chen, H.C.,Lo, Y.C.,Chen, C.P.,Barber, G.N.,Chuah, M.L.,Liang, Z.X.,Chou, S.H. Novel c-di-GMP recognition modes of the mouse innate immune adaptor protein STING Acta Crystallogr.,Sect.D, 69:352-366, 2013 Cited by PubMed Abstract: The mammalian ER protein STING (stimulator of interferon genes; also known as MITA, ERIS, MPYS or TMEM173) is an adaptor protein that links the detection of cytosolic dsDNA to the activation of TANK-binding kinase 1 (TBK1) and its downstream transcription factor interferon regulatory factor 3 (IFN3). Recently, STING itself has been found to be the direct receptor of bacterial c-di-GMP, and crystal structures of several human STING C-terminal domain (STING-CTD) dimers in the apo form or in complex with c-di-GMP have been published. Here, a novel set of structures of mouse STING-CTD (mSTING(137-344)) in apo and complex forms determined from crystals obtained under different crystallization conditions are reported. These novel closed-form structures exhibited considerable differences from previously reported open-form human STING-CTD structures. The novel mSTING structures feature extensive interactions between the two monomers, a unique asymmetric c-di-GMP molecule with one guanine base in an unusual syn conformation that is well accommodated in the dimeric interface with many direct specific interactions and two unexpected equivalent secondary peripheral c-di-GMP binding sites. Replacement of the amino acids crucial for specific c-di-GMP binding in mSTING significantly changes the ITC titration profiles and reduces the IFN-β reporter luciferase activity. Taken together, these results reveal a more stable c-di-GMP binding mode of STING proteins that could serve as a template for rational drug design to stimulate interferon production by mammalian cells. PubMed: 23519410DOI: 10.1107/S0907444912047269 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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