4yp1
From Proteopedia
(Difference between revisions)
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4yp1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YP1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YP1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4yp1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YP1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YP1 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2BA:(2R,3R,3AS,5R,7AR,9R,10R,10AS,12R,14AR)-2,9-BIS(6-AMINO-9H-PURIN-9-YL)OCTAHYDRO-2H,7H-DIFURO[3,2-D 3,2-J][1,3,7,9,2,8]TETRAOXADIPHOSPHACYCLODODECINE-3,5,10,12-TETROL+5,12-DIOXIDE'>2BA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2BA:(2R,3R,3AS,5R,7AR,9R,10R,10AS,12R,14AR)-2,9-BIS(6-AMINO-9H-PURIN-9-YL)OCTAHYDRO-2H,7H-DIFURO[3,2-D 3,2-J][1,3,7,9,2,8]TETRAOXADIPHOSPHACYCLODODECINE-3,5,10,12-TETROL+5,12-DIOXIDE'>2BA</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yp1 OCA], [https://pdbe.org/4yp1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yp1 RCSB], [https://www.ebi.ac.uk/pdbsum/4yp1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yp1 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yp1 OCA], [https://pdbe.org/4yp1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yp1 RCSB], [https://www.ebi.ac.uk/pdbsum/4yp1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yp1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://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> | [https://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 == | ||
| - | Cyclic di-AMP (c-di-AMP) is a relatively new member of the family of bacterial cyclic dinucleotide second messengers. It has attracted significant attention in recent years because of the abundant roles it plays in a variety of Gram-positive bacteria. The structural features that allow diverse bacterial proteins to bind c-di-AMP are not fully understood. Here we report the biophysical and structural studies of c-di-AMP in complex with a bacterial cation-proton antiporter (CpaA) RCK (regulator of the conductance of K(+)) protein from Staphylococcus aureus (Sa). The crystal structure of the SaCpaA_RCK C-terminal domain (CTD) in complex with c-di-AMP was determined to a resolution of 1.81 A. This structure revealed two well-liganded water molecules, each interacting with one of the adenine bases by a unique H2Olp-pi interaction to stabilize the complex. Sequence blasting using the SaCpaA_RCK primary sequence against the bacterial genome database returned many CpaA analogues, and alignment of these sequences revealed that the active site residues are all well-conserved, indicating a universal c-di-AMP binding mode for CpaA_RCK. A proteoliposome activity assay using the full-length SaCpaA membrane protein indicated that c-di-AMP binding alters its antiporter activity by approximately 40%. A comparison of this structure to all other reported c-di-AMP-receptor complex structures revealed that c-di-AMP binds to receptors in either a "U-shape" or "V-shape" mode. The two adenine rings are stabilized in the inner interaction zone by a variety of CH-pi, cation-pi, backbone-pi, or H2Olp-pi interaction, but more commonly in the outer interaction zone by hydrophobic CH-pi or pi-pi interaction. The structures determined to date provide an understanding of the mechanisms by which a single c-di-AMP can interact with a variety of receptor proteins, and how c-di-AMP binds receptor proteins in a special way different from that of c-di-GMP. | ||
| - | |||
| - | Structural Insights into the Distinct Binding Mode of Cyclic Di-AMP with SaCpaA_RCK.,Chin KH, Liang JM, Yang JG, Shih MS, Tu ZL, Wang YC, Sun XH, Hu NJ, Liang ZX, Dow JM, Ryan RP, Chou SH Biochemistry. 2015 Aug 11;54(31):4936-51. doi: 10.1021/acs.biochem.5b00633. Epub , 2015 Jul 27. PMID:26171638<ref>PMID:26171638</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4yp1" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Misting with CDA
| |||||||||||
Categories: Large Structures | Mus musculus | Chen CK | Chin KH | Chou SH | Tu ZI
