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3e07

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Revision as of 11:25, 25 December 2014

Crystal structure of spatzle cystine knot

Structural highlights

3e07 is a 2 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	spz (Drosophila melanogaster)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The Drosophila Spatzle protein, involved in the embryonic development of the dorsal-ventral axis and in the adult immune response, is expressed as a proprotein and is activated by the serine proteinases Easter or Spatzle-processing enzyme. Proteolytic cleavage generates a 106-amino acid COOH-terminal fragment, C106, homologous to the mature form of nerve growth factor NGF, a cystine knot protein. Through alternative splicing, the Spatzle gene encodes for several isoforms that (with one exception, the "propeptide isoform") share C106 but differ in the prosequence. Three isoforms have been expressed recombinantly in Escherichia coli strains. The propeptide isoform could be expressed in soluble form and is unstructured according to CD and NMR measurements. Dimeric full-length Spatzle isoforms have been refolded from insoluble inclusion bodies and are able to rescue Spatzle-deficient embryos. Although the two full-length isoforms exhibit similar far-UV CD spectra, large differences in tryptophan fluorescence quenching by the respective pro-parts are observed. Both full-length isoforms exhibited highly cooperative folding transitions. Proteolytic digestion using trypsin resulted in C106, whose unfolding exhibits lower thermodynamic stability and cooperativity compared with the full-length proteins. The structure of C106 reveals a T-shaped dimer with significant differences to NGF and a deep internal cavity. Substantial beta-sheet formation is observed between the two monomers, whereas a long loop containing the single tryptophan residue is disordered in the crystals. Our results suggest that the propeptides stabilize the tertiary structure of the "mature" Spatzle cystine knot.

Biophysical characterization of refolded Drosophila Spatzle, a cystine knot protein, reveals distinct properties of three isoforms.,Hoffmann A, Funkner A, Neumann P, Juhnke S, Walther M, Schierhorn A, Weininger U, Balbach J, Reuter G, Stubbs MT J Biol Chem. 2008 Nov 21;283(47):32598-609. Epub 2008 Sep 12. PMID:18790733^[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
↑ Hoffmann A, Funkner A, Neumann P, Juhnke S, Walther M, Schierhorn A, Weininger U, Balbach J, Reuter G, Stubbs MT. Biophysical characterization of refolded Drosophila Spatzle, a cystine knot protein, reveals distinct properties of three isoforms. J Biol Chem. 2008 Nov 21;283(47):32598-609. Epub 2008 Sep 12. PMID:18790733 doi:10.1074/jbc.M801815200

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/3e07"

@@ Line 7: / Line 7: @@
 <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=3e07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e07 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3e07 RCSB], [http://www.ebi.ac.uk/pdbsum/3e07 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/SPZ_DROME 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.<ref>PMID:8124709</ref> <ref>PMID:11212919</ref> <ref>PMID:8808632</ref> <ref>PMID:12872120</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3e07

From Proteopedia

Revision as of 11:25, 25 December 2014

Crystal structure of spatzle cystine knot

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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