This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

5ur7

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:39, 29 November 2017

Crystal structure of engineered CCL20 disulfide locked dimer

Structural highlights

5ur7 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	CCL20, LARC, MIP3A, SCYA20 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CCL20_HUMAN] Chemotactic factor that attracts lymphocytes and, slightly, neutrophils, but not monocytes. Inhibits proliferation of myeloid progenitors in colony formation assays. May be involved in formation and function of the mucosal lymphoid tissues by attracting lymphocytes and dendritic cells towards epithelial cells. C-terminal processed forms have been shown to be equally chemotactically active for leukocytes. Possesses antibacterial activity E.coli ATCC 25922 and S.aureus ATCC 29213.^[1]

Publication Abstract from PubMed

Psoriasis is a chronic inflammatory skin disease characterized by the infiltration of T cell and other immune cells to the skin in response to injury or autoantigens. Conventional, as well as unconventional, gammadelta T cells are recruited to the dermis and epidermis by CCL20 and other chemokines. Together with its receptor CCR6, CCL20 plays a critical role in the development of psoriasiform dermatitis in mouse models. We screened a panel of CCL20 variants designed to form dimers stabilized by intermolecular disulfide bonds. A single-atom substitution yielded a CCL20 variant (CCL20 S64C) that acted as a partial agonist for the chemokine receptor CCR6. CCL20 S64C bound CCR6 and induced intracellular calcium release, consistent with G-protein activation, but exhibited minimal chemotactic activity. Instead, CCL20 S64C inhibited CCR6-mediated T cell migration with nominal impact on other chemokine receptor signaling. When given in an IL-23-dependent mouse model for psoriasis, CCL20 S64C prevented psoriatic inflammation and the up-regulation of IL-17A and IL-22. Our results validate CCR6 as a tractable therapeutic target for psoriasis and demonstrate the value of CCL20 S64C as a lead compound.

Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model.,Getschman AE, Imai Y, Larsen O, Peterson FC, Wu X, Rosenkilde MM, Hwang ST, Volkman BF Proc Natl Acad Sci U S A. 2017 Nov 6. pii: 201704958. doi:, 10.1073/pnas.1704958114. PMID:29109267^[2]

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

References

↑ Hoover DM, Boulegue C, Yang D, Oppenheim JJ, Tucker K, Lu W, Lubkowski J. The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins. J Biol Chem. 2002 Oct 4;277(40):37647-54. Epub 2002 Jul 30. PMID:12149255 doi:10.1074/jbc.M203907200
↑ Getschman AE, Imai Y, Larsen O, Peterson FC, Wu X, Rosenkilde MM, Hwang ST, Volkman BF. Protein engineering of the chemokine CCL20 prevents psoriasiform dermatitis in an IL-23-dependent murine model. Proc Natl Acad Sci U S A. 2017 Nov 6. pii: 201704958. doi:, 10.1073/pnas.1704958114. PMID:29109267 doi:http://dx.doi.org/10.1073/pnas.1704958114

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/5ur7"

@@ Line 3: / Line 3: @@
 <StructureSection load='5ur7' size='340' side='right' caption='[[5ur7]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ur7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UR7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UR7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ur7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UR7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UR7 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCL20, LARC, MIP3A, SCYA20 ([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=5ur7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ur7 OCA], [http://pdbe.org/5ur7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ur7 RCSB], [http://www.ebi.ac.uk/pdbsum/5ur7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ur7 ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Getschman, A E]]
 [[Category: Peterson, F C]]

5ur7

From Proteopedia

Revision as of 07:39, 29 November 2017

Crystal structure of engineered CCL20 disulfide locked dimer

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox