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4kby

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Revision as of 23:55, 24 December 2014

mSTING/c-di-GMP

Structural highlights

4kby is a 2 chain structure with sequence from Mus musculus. This structure supersedes the now removed PDB entry 4g4d. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4kc0
Gene:	Tmem173, Eris Mita, Mpys, Sting (Mus musculus)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[STING_MOUSE] Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

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-beta 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.

Novel c-di-GMP recognition modes of the mouse innate immune adaptor protein STING.,Chin KH, Tu ZL, Su YC, Yu YJ, Chen HC, Lo YC, Chen CP, Barber GN, Chuah ML, Liang ZX, Chou SH Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):352-66. doi:, 10.1107/S0907444912047269. Epub 2013 Feb 16. PMID:23519410^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhong B, Yang Y, Li S, Wang YY, Li Y, Diao F, Lei C, He X, Zhang L, Tien P, Shu HB. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity. 2008 Oct 17;29(4):538-50. doi: 10.1016/j.immuni.2008.09.003. Epub 2008 , Sep 25. PMID:18818105 doi:10.1016/j.immuni.2008.09.003
↑ Jin L, Waterman PM, Jonscher KR, Short CM, Reisdorph NA, Cambier JC. MPYS, a novel membrane tetraspanner, is associated with major histocompatibility complex class II and mediates transduction of apoptotic signals. Mol Cell Biol. 2008 Aug;28(16):5014-26. doi: 10.1128/MCB.00640-08. Epub 2008 Jun , 16. PMID:18559423 doi:10.1128/MCB.00640-08
↑ Ishikawa H, Barber GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature. 2008 Oct 2;455(7213):674-8. doi: 10.1038/nature07317. Epub 2008 Aug 24. PMID:18724357 doi:10.1038/nature07317
↑ Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature. 2009 Oct 8;461(7265):788-92. doi: 10.1038/nature08476. Epub 2009 Sep 23. PMID:19776740 doi:10.1038/nature08476
↑ Sun W, Li Y, Chen L, Chen H, You F, Zhou X, Zhou Y, Zhai Z, Chen D, Jiang Z. ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization. Proc Natl Acad Sci U S A. 2009 May 26;106(21):8653-8. doi:, 10.1073/pnas.0900850106. Epub 2009 May 11. PMID:19433799 doi:10.1073/pnas.0900850106
↑ Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 2013 Feb 15;339(6121):826-30. doi: 10.1126/science.1229963. Epub 2012, Dec 20. PMID:23258412 doi:10.1126/science.1229963
↑ Chin KH, Tu ZL, Su YC, Yu YJ, Chen HC, Lo YC, Chen CP, Barber GN, Chuah ML, Liang ZX, Chou SH. Novel c-di-GMP recognition modes of the mouse innate immune adaptor protein STING. Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):352-66. doi:, 10.1107/S0907444912047269. Epub 2013 Feb 16. PMID:23519410 doi:10.1107/S0907444912047269

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4kby"

@@ Line 8: / Line 8: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4kby FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kby OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kby RCSB], [http://www.ebi.ac.uk/pdbsum/4kby PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/STING_MOUSE STING_MOUSE]] Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway.<ref>PMID:18818105</ref> <ref>PMID:18559423</ref> <ref>PMID:18724357</ref> <ref>PMID:19776740</ref> <ref>PMID:19433799</ref> <ref>PMID:23258412</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4kby

From Proteopedia

Revision as of 23:55, 24 December 2014

mSTING/c-di-GMP

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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