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5gs0

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Revision as of 06:41, 20 May 2020

Crystal structure of the complex of TLR3 and bi-specific diabody

Structural highlights

5gs0 is a 10 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	5gru, 5grv, 5grw, 5grx, 5gry, 5grz, 5gs1, 5gs2, 5gs3
Gene:	TLR3 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TLR3_HUMAN] Defects in TLR3 are associated with herpes simplex encephalitis type 2 (HSE2) [MIM:613002]. HSE is a rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. Note=TLR3 mutations predispose otherwise healthy individuals to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced immune defense against viral infection in the central nervous system.^[1]

Function

[TLR3_HUMAN] Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

Building a sophisticated protein nano-assembly requires a method for linking protein components in a predictable and stable structure. Diabodies are engineered antibody fragments that are composed of two Fv domains connected by short peptide linkers. They are attractive candidates for mediators in assembling protein nano-structures because they can simultaneously bind to two different proteins and are rigid enough to be crystallized. However, comparison of previous crystal structures demonstrates that there is substantial structural diversity in the Fv interface region of diabodies and, therefore, reliable prediction of its structure is not trivial. Here, we present the crystal structures of ten mono- and bi-specific diabodies. We found that changing an arginine residue in the Fv interface to threonine greatly reduced the structural diversity of diabodies. We also found that one of the bispecific diabodies underwent an unexpected process of chain swapping yielding a non-functional monospecific diabody. In order to further reduce structural flexibility and prevent chain shuffling, we introduced disulfide bridges in the Fv interface regions. The disulfide-bridged diabodies have rigid and predictable structures and may have applications in crystallizing proteins, analyzing cryo-electron microscopic images and building protein nano-assemblies.

Crystal structures of mono- and bi-specific diabodies and reduction of their structural flexibility by introduction of disulfide bridges at the Fv interface.,Kim JH, Song DH, Youn SJ, Kim JW, Cho G, Kim SC, Lee H, Jin MS, Lee JO Sci Rep. 2016 Sep 29;6:34515. doi: 10.1038/srep34515. PMID:27682821^[8]

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

References

↑ Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, Segal D, Sancho-Shimizu V, Lorenzo L, Puel A, Picard C, Chapgier A, Plancoulaine S, Titeux M, Cognet C, von Bernuth H, Ku CL, Casrouge A, Zhang XX, Barreiro L, Leonard J, Hamilton C, Lebon P, Heron B, Vallee L, Quintana-Murci L, Hovnanian A, Rozenberg F, Vivier E, Geissmann F, Tardieu M, Abel L, Casanova JL. TLR3 deficiency in patients with herpes simplex encephalitis. Science. 2007 Sep 14;317(5844):1522-7. PMID:17872438 doi:317/5844/1522
↑ de Bouteiller O, Merck E, Hasan UA, Hubac S, Benguigui B, Trinchieri G, Bates EE, Caux C. Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH. J Biol Chem. 2005 Nov 18;280(46):38133-45. Epub 2005 Sep 6. PMID:16144834 doi:M507163200
↑ Johnsen IB, Nguyen TT, Ringdal M, Tryggestad AM, Bakke O, Lien E, Espevik T, Anthonsen MW. Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling. EMBO J. 2006 Jul 26;25(14):3335-46. Epub 2006 Jul 6. PMID:16858407 doi:7601222
↑ Bell JK, Askins J, Hall PR, Davies DR, Segal DM. The dsRNA binding site of human Toll-like receptor 3. Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8792-7. Epub 2006 May 23. PMID:16720699 doi:10.1073/pnas.0603245103
↑ Sarkar SN, Elco CP, Peters KL, Chattopadhyay S, Sen GC. Two tyrosine residues of Toll-like receptor 3 trigger different steps of NF-kappa B activation. J Biol Chem. 2007 Feb 9;282(6):3423-7. Epub 2006 Dec 18. PMID:17178723 doi:C600226200
↑ Leonard JN, Ghirlando R, Askins J, Bell JK, Margulies DH, Davies DR, Segal DM. The TLR3 signaling complex forms by cooperative receptor dimerization. Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):258-63. doi: 10.1073/pnas.0710779105., Epub 2008 Jan 2. PMID:18172197 doi:10.1073/pnas.0710779105
↑ Bell JK, Botos I, Hall PR, Askins J, Shiloach J, Segal DM, Davies DR. The molecular structure of the Toll-like receptor 3 ligand-binding domain. Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10976-80. Epub 2005 Jul 25. PMID:16043704
↑ Kim JH, Song DH, Youn SJ, Kim JW, Cho G, Kim SC, Lee H, Jin MS, Lee JO. Crystal structures of mono- and bi-specific diabodies and reduction of their structural flexibility by introduction of disulfide bridges at the Fv interface. Sci Rep. 2016 Sep 29;6:34515. doi: 10.1038/srep34515. PMID:27682821 doi:http://dx.doi.org/10.1038/srep34515

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5gs0"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the complex of TLR3 and bi-specific diabody==
-<StructureSection load='5gs0' size='340' side='right' caption='[[5gs0]], [[Resolution|resolution]] 3.27&Aring;' scene=''>
+<StructureSection load='5gs0' size='340' side='right'caption='[[5gs0]], [[Resolution|resolution]] 3.27&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5gs0]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GS0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GS0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5gs0]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GS0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5GS0 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5gru|5gru]], [[5grv|5grv]], [[5grw|5grw]], [[5grx|5grx]], [[5gry|5gry]], [[5grz|5grz]], [[5gs1|5gs1]], [[5gs2|5gs2]], [[5gs3|5gs3]]</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=5gs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gs0 OCA], [http://pdbe.org/5gs0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gs0 RCSB], [http://www.ebi.ac.uk/pdbsum/5gs0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gs0 ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TLR3 ([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://proteopedia.org/fgij/fg.htm?mol=5gs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gs0 OCA], [http://pdbe.org/5gs0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gs0 RCSB], [http://www.ebi.ac.uk/pdbsum/5gs0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gs0 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 </div>
 <div class="pdbe-citations 5gs0" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Toll-like Receptor 3D structures|Toll-like Receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Cho, G]]
 [[Category: Kim, J H]]

5gs0

From Proteopedia

Revision as of 06:41, 20 May 2020

Crystal structure of the complex of TLR3 and bi-specific diabody

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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