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4bv4

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Revision as of 13:33, 15 March 2017

Structure and allostery in Toll-Spatzle recognition

Structural highlights

4bv4 is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[SPZ_DROME] Component of the extracellular signaling pathway that establishes the dorsal-ventral pathway of the embryo. Three proteases; ndl, gd and snk process easter to create active easter. Active easter defines cell identities along the dorsal-ventral continuum by activating the spz ligand for the Tl receptor in the ventral region of the embryo. Spz C-106 in the hemolymph controls expression of the antifungal peptide Drosomycin (Drs) by acting as a ligand of Tl and inducing an intracellular signaling pathway.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Drosophila Toll functions in embryonic development and innate immunity and is activated by an endogenous ligand, Spatzle (Spz). The related Toll-like receptors in vertebrates also function in immunity but are activated directly by pathogen-associated molecules such as bacterial endotoxin. Here, we present the crystal structure at 2.35-A resolution of dimeric Spz bound to a Toll ectodomain encompassing the first 13 leucine-rich repeats. The cystine knot of Spz binds the concave face of the Toll leucine-rich repeat solenoid in an area delineated by N-linked glycans and induces a conformational change. Mutagenesis studies confirm that the interface observed in the crystal structure is relevant for signaling. The asymmetric binding mode of Spz to Toll is similar to that of nerve growth factor (NGF) in complex with the p75 neurotrophin receptor but is distinct from that of microbial ligands bound to the Toll-like receptors. Overall, this study indicates an allosteric signaling mechanism for Toll in which ligand binding to the N terminus induces a conformational change that couples to homodimerization of juxtamembrane structures in the Toll ectodomain C terminus.

Cytokine Spatzle binds to the Drosophila immunoreceptor Toll with a neurotrophin-like specificity and couples receptor activation.,Lewis M, Arnot CJ, Beeston H, McCoy A, Ashcroft AE, Gay NJ, Gangloff M Proc Natl Acad Sci U S A. 2013 Nov 26. PMID:24282309^[5]

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

References

↑ Morisato D, Anderson KV. The spatzle gene encodes a component of the extracellular signaling pathway establishing the dorsal-ventral pattern of the Drosophila embryo. Cell. 1994 Feb 25;76(4):677-88. PMID:8124709
↑ DeLotto Y, Smith C, DeLotto R. Multiple isoforms of the Drosophila Spatzle protein are encoded by alternatively spliced maternal mRNAs in the precellular blastoderm embryo. Mol Gen Genet. 2001 Jan;264(5):643-52. PMID:11212919
↑ Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996 Sep 20;86(6):973-83. PMID:8808632
↑ Weber AN, Tauszig-Delamasure S, Hoffmann JA, Lelievre E, Gascan H, Ray KP, Morse MA, Imler JL, Gay NJ. Binding of the Drosophila cytokine Spatzle to Toll is direct and establishes signaling. Nat Immunol. 2003 Aug;4(8):794-800. Epub 2003 Jul 20. PMID:12872120 doi:http://dx.doi.org/10.1038/ni955
↑ Lewis M, Arnot CJ, Beeston H, McCoy A, Ashcroft AE, Gay NJ, Gangloff M. Cytokine Spatzle binds to the Drosophila immunoreceptor Toll with a neurotrophin-like specificity and couples receptor activation. Proc Natl Acad Sci U S A. 2013 Nov 26. PMID:24282309 doi:http://dx.doi.org/10.1073/pnas.1317002110

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/4bv4"

@@ Line 3: / Line 3: @@
 <StructureSection load='4bv4' size='340' side='right' caption='[[4bv4]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4bv4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BV4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BV4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4bv4]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BV4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BV4 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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
+</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>
 <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=4bv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bv4 OCA], [http://pdbe.org/4bv4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bv4 RCSB], [http://www.ebi.ac.uk/pdbsum/4bv4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bv4 ProSAT]</span></td></tr>
 </table>
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Drome]]
 [[Category: Arnot, C J]]
 [[Category: Ashcroft, A E]]

4bv4

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Revision as of 13:33, 15 March 2017

Structure and allostery in Toll-Spatzle recognition

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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