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6l9w

From Proteopedia

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Crystal structure of mouse TIFA (T9E/C36S mutant)

Structural highlights

6l9w is a 6 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TIFA_MOUSE Adapter molecule that plays a key role in the activation of proinflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (PubMed:11798190). Promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism (By similarity). TIFA-dependent innate immune response is triggered by ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria: ADP-Heptose is recognized by ALPK1, which phosphorylates TIFA at Thr-9, leading to TIFA homooligomerization and subsequent activation of proinflammatory NF-kappa-B signaling (By similarity).[UniProtKB:Q96CG3]^[1]

Publication Abstract from PubMed

TRAF-interacting protein with a forkhead-associated (FHA) domain (TIFA), originally identified as an adaptor protein of TRAF6, has recently been shown to be involved in innate immunity, induced by a pathogen-associated molecular pattern (PAMP). ADP-beta-D-manno-heptose, a newly identified PAMP, binds to alpha-kinase 1 (ALPK1) and activates its kinase activity to phosphorylate TIFA. Phosphorylation triggers TIFA oligomerisation and formation of a subsequent TIFA-TRAF6 oligomeric complex for ubiquitination of TRAF6, eventually leading to NF-kappaB activation. However, the structural basis of TIFA-dependent TRAF6 signalling, especially oligomer formation of the TIFA-TRAF6 complex remains unknown. In the present study, we determined the crystal structures of mouse TIFA and two TIFA mutants-Thr9 mutated to either Asp or Glu to mimic the phosphorylation state-to obtain the structural information for oligomer formation of the TIFA-TRAF6 complex. Crystal structures show the dimer formation of mouse TIFA to be similar to that of human TIFA, which was previously reported. This dimeric structure is consistent with the solution structure obtained from small angle X-ray scattering analysis. In addition to the structural analysis, we examined the molecular assembly of TIFA and the TIFA-TRAF6 complex by size-exclusion chromatography, and suggested a model for the TIFA-TRAF6 signalling complex.

Structural analysis of TIFA: Insight into TIFA-dependent signal transduction in innate immunity.,Nakamura T, Hashikawa C, Okabe K, Yokote Y, Chirifu M, Toma-Fukai S, Nakamura N, Matsuo M, Kamikariya M, Okamoto Y, Gohda J, Akiyama T, Semba K, Ikemizu S, Otsuka M, Inoue JI, Yamagata Y Sci Rep. 2020 Mar 20;10(1):5152. doi: 10.1038/s41598-020-61972-6. PMID:32198460^[2]

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

References

↑ Kanamori M, Suzuki H, Saito R, Muramatsu M, Hayashizaki Y. T2BP, a novel TRAF2 binding protein, can activate NF-kappaB and AP-1 without TNF stimulation. Biochem Biophys Res Commun. 2002 Jan 25;290(3):1108-13. doi:, 10.1006/bbrc.2001.6315. PMID:11798190 doi:http://dx.doi.org/10.1006/bbrc.2001.6315
↑ Nakamura T, Hashikawa C, Okabe K, Yokote Y, Chirifu M, Toma-Fukai S, Nakamura N, Matsuo M, Kamikariya M, Okamoto Y, Gohda J, Akiyama T, Semba K, Ikemizu S, Otsuka M, Inoue JI, Yamagata Y. Structural analysis of TIFA: Insight into TIFA-dependent signal transduction in innate immunity. Sci Rep. 2020 Mar 20;10(1):5152. doi: 10.1038/s41598-020-61972-6. PMID:32198460 doi:http://dx.doi.org/10.1038/s41598-020-61972-6

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6l9w"

Categories: Large Structures | Mus musculus | Nakamura T | Yamagata Y

@@ Line 3: / Line 3: @@
 <StructureSection load='6l9w' size='340' side='right'caption='[[6l9w]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6l9w]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L9W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6L9W FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6l9w]] is a 6 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=6L9W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L9W FirstGlance]. <br>
-</td></tr><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=6l9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l9w OCA], [http://pdbe.org/6l9w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l9w RCSB], [http://www.ebi.ac.uk/pdbsum/6l9w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l9w ProSAT]</span></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]] 2.9&#8491;</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=6l9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l9w OCA], [https://pdbe.org/6l9w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l9w RCSB], [https://www.ebi.ac.uk/pdbsum/6l9w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l9w ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/TIFA_MOUSE TIFA_MOUSE]] Adapter molecule that plays a key role in the activation of proinflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (PubMed:11798190). Promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism (By similarity). TIFA-dependent innate immune response is triggered by ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria: ADP-Heptose is recognized by ALPK1, which phosphorylates TIFA at Thr-9, leading to TIFA homooligomerization and subsequent activation of proinflammatory NF-kappa-B signaling (By similarity).[UniProtKB:Q96CG3]<ref>PMID:11798190</ref>
+[https://www.uniprot.org/uniprot/TIFA_MOUSE TIFA_MOUSE] Adapter molecule that plays a key role in the activation of proinflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (PubMed:11798190). Promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism (By similarity). TIFA-dependent innate immune response is triggered by ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria: ADP-Heptose is recognized by ALPK1, which phosphorylates TIFA at Thr-9, leading to TIFA homooligomerization and subsequent activation of proinflammatory NF-kappa-B signaling (By similarity).[UniProtKB:Q96CG3]<ref>PMID:11798190</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Nakamura, T]]
+[[Category: Mus musculus]]
-[[Category: Yamagata, Y]]
+[[Category: Nakamura T]]
-[[Category: Fha domain]]
+[[Category: Yamagata Y]]
-[[Category: Signaling protein]]

6l9w

From Proteopedia

Current revision

Crystal structure of mouse TIFA (T9E/C36S mutant)

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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