6aci

From Proteopedia

(Difference between revisions)

Revision as of 07:20, 26 June 2019

Crystal structure of EPEC effector NleB in complex with FADD death domain

Structural highlights

6aci is a 2 chain structure with sequence from Eco27 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	6e66, 6ac0, 6ac5
Gene:	E2348C_3231 (ECO27), FADD, MORT1, GIG3 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[FADD_HUMAN] Defects in FADD are the cause of infections recurrent associated with encephalopathy hepatic dysfunction and cardiovascular malformations (IEHDCM) [MIM:613759]. A condition with biological features of autoimmune lymphoproliferative syndrome such as high-circulating CD4(-)CD8(-)TCR-alpha-beta(+) T-cell counts, and elevated IL10 and FASL levels. Affected individuals suffer from recurrent, stereotypical episodes of fever, encephalopathy, and mild liver dysfunction sometimes accompanied by generalized seizures. The episodes can be triggered by varicella zoster virus (VZV), measles mumps rubella (MMR) attenuated vaccine, parainfluenza virus, and Epstein-Barr virus (EBV).^[1]

Function

[FADD_HUMAN] Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis. Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling.^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Enteropathogenic E. coli NleB and related type III effectors catalyze arginine GlcNAcylation of death domain (DD) proteins to block host defense, but the underlying mechanism is unknown. Here we solve crystal structures of NleB alone and in complex with FADD-DD, UDP, and Mn(2+) as well as NleB-GlcNAcylated DDs of TRADD and RIPK1. NleB adopts a GT-A fold with a unique helix-pair insertion to hold FADD-DD; the interface contacts explain the selectivity of NleB for certain DDs. The acceptor arginine is fixed into a cleft, in which Glu253 serves as a base to activate the guanidinium. Analyses of the enzyme-substrate complex and the product structures reveal an inverting sugar-transfer reaction and a detailed catalytic mechanism. These structural insights are validated by mutagenesis analyses of NleB-mediated GlcNAcylation in vitro and its function in mouse infection. Our study builds a structural framework for understanding of NleB-catalyzed arginine GlcNAcylation of host death domain.

Structural and Functional Insights into Host Death Domains Inactivation by the Bacterial Arginine GlcNAcyltransferase Effector.,Ding J, Pan X, Du L, Yao Q, Xue J, Yao H, Wang DC, Li S, Shao F Mol Cell. 2019 Apr 3. pii: S1097-2765(19)30232-1. doi:, 10.1016/j.molcel.2019.03.028. PMID:30979585^[6]

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

References

↑ Bolze A, Byun M, McDonald D, Morgan NV, Abhyankar A, Premkumar L, Puel A, Bacon CM, Rieux-Laucat F, Pang K, Britland A, Abel L, Cant A, Maher ER, Riedl SJ, Hambleton S, Casanova JL. Whole-exome-sequencing-based discovery of human FADD deficiency. Am J Hum Genet. 2010 Dec 10;87(6):873-81. doi: 10.1016/j.ajhg.2010.10.028. Epub, 2010 Nov 25. PMID:21109225 doi:10.1016/j.ajhg.2010.10.028
↑ Bolze A, Byun M, McDonald D, Morgan NV, Abhyankar A, Premkumar L, Puel A, Bacon CM, Rieux-Laucat F, Pang K, Britland A, Abel L, Cant A, Maher ER, Riedl SJ, Hambleton S, Casanova JL. Whole-exome-sequencing-based discovery of human FADD deficiency. Am J Hum Genet. 2010 Dec 10;87(6):873-81. doi: 10.1016/j.ajhg.2010.10.028. Epub, 2010 Nov 25. PMID:21109225 doi:10.1016/j.ajhg.2010.10.028
↑ Carrington PE, Sandu C, Wei Y, Hill JM, Morisawa G, Huang T, Gavathiotis E, Wei Y, Werner MH. The structure of FADD and its mode of interaction with procaspase-8. Mol Cell. 2006 Jun 9;22(5):599-610. PMID:16762833 doi:10.1016/j.molcel.2006.04.018
↑ Scott FL, Stec B, Pop C, Dobaczewska MK, Lee JJ, Monosov E, Robinson H, Salvesen GS, Schwarzenbacher R, Riedl SJ. The Fas-FADD death domain complex structure unravels signalling by receptor clustering. Nature. 2009 Feb 19;457(7232):1019-22. Epub 2008 Dec 31. PMID:19118384 doi:nature07606
↑ Wang L, Yang JK, Kabaleeswaran V, Rice AJ, Cruz AC, Park AY, Yin Q, Damko E, Jang SB, Raunser S, Robinson CV, Siegel RM, Walz T, Wu H. The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations. Nat Struct Mol Biol. 2010 Nov;17(11):1324-9. Epub 2010 Oct 10. PMID:20935634 doi:10.1038/nsmb.1920
↑ Ding J, Pan X, Du L, Yao Q, Xue J, Yao H, Wang DC, Li S, Shao F. Structural and Functional Insights into Host Death Domains Inactivation by the Bacterial Arginine GlcNAcyltransferase Effector. Mol Cell. 2019 Apr 3. pii: S1097-2765(19)30232-1. doi:, 10.1016/j.molcel.2019.03.028. PMID:30979585 doi:http://dx.doi.org/10.1016/j.molcel.2019.03.028

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='6aci' size='340' side='right'caption='[[6aci]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6aci]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ACI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ACI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6aci]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Eco27 Eco27] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ACI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ACI FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6e66|6e66]], [[6ac0|6ac0]], [[6ac5|6ac5]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">E2348C_3231 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=574521 ECO27]), FADD, MORT1, GIG3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6aci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aci OCA], [http://pdbe.org/6aci PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aci RCSB], [http://www.ebi.ac.uk/pdbsum/6aci PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aci ProSAT]</span></td></tr>
 </table>
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Eco27]]
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Ding, J]]

6aci

From Proteopedia

Revision as of 07:20, 26 June 2019

Crystal structure of EPEC effector NleB in complex with FADD death domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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