2kec

From Proteopedia

(Difference between revisions)

Current revision

Structure of SDF-1/CXCL12

Structural highlights

2kec is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SDF1_HUMAN Chemoattractant active on T-lymphocytes, monocytes, but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. Also binds to another C-X-C chemokine receptor CXCR7, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and CXCR7, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of CXCR7 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

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 chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) directs leukocyte migration, stem cell homing, and cancer metastasis through activation of CXCR4, which is also a coreceptor for T-tropic HIV-1. Recently, SDF-1 was shown to play a protective role after myocardial infarction, and the protein is a candidate for development of new anti-ischemic compounds. SDF-1 is monomeric at nanomolar concentrations but binding partners promote self-association at higher concentrations to form a typical CXC chemokine homodimer. Two NMR structures have been reported for the SDF-1 monomer, but only one matches the conformation observed in a series of dimeric crystal structures. In the other model, the C-terminal helix is tilted at an angle incompatible with SDF-1 dimerization. Using a rat heart explant model for ischemia/reperfusion injury, we found that dimeric SDF-1 exerts no cardioprotective effect, suggesting that the active species is monomeric. To resolve the discrepancy between existing models, we solved the NMR structure of the SDF-1 monomer in different solution conditions. Irrespective of pH and buffer composition, the C-terminal helix remains tilted at an angle with no evidence for the perpendicular arrangement. Furthermore, we find that phospholipid bicelles promote dimerization that necessarily shifts the helix to the perpendicular orientation, yielding dipolar couplings that are incompatible with the NOE distance constraints. We conclude that interactions with the alignment medium biased the previous structure, masking flexibility in the helix position that may be essential for the distinct functional properties of the SDF-1 monomer.

Monomeric structure of the cardioprotective chemokine SDF-1/CXCL12.,Veldkamp CT, Ziarek JJ, Su J, Basnet H, Lennertz R, Weiner JJ, Peterson FC, Baker JE, Volkman BF Protein Sci. 2009 Jul;18(7):1359-69. PMID:19551879^[7]

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

References

↑ Oberlin E, Amara A, Bachelerie F, Bessia C, Virelizier JL, Arenzana-Seisdedos F, Schwartz O, Heard JM, Clark-Lewis I, Legler DF, Loetscher M, Baggiolini M, Moser B. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature. 1996 Aug 29;382(6594):833-5. PMID:8752281 doi:10.1038/382833a0
↑ Moepps B, Braun M, Knopfle K, Dillinger K, Knochel W, Gierschik P. Characterization of a Xenopus laevis CXC chemokine receptor 4: implications for hematopoietic cell development in the vertebrate embryo. Eur J Immunol. 2000 Oct;30(10):2924-34. PMID:11069075
↑ Braun M, Wunderlin M, Spieth K, Knochel W, Gierschik P, Moepps B. Xenopus laevis Stromal cell-derived factor 1: conservation of structure and function during vertebrate development. J Immunol. 2002 Mar 1;168(5):2340-7. PMID:11859124
↑ Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F. The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem. 2005 Oct 21;280(42):35760-6. Epub 2005 Aug 17. PMID:16107333 doi:M508234200
↑ Malik M, Chen YY, Kienzle MF, Tomkowicz BE, Collman RG, Ptasznik A. Monocyte migration and LFA-1-mediated attachment to brain microvascular endothelia is regulated by SDF-1 alpha through Lyn kinase. J Immunol. 2008 Oct 1;181(7):4632-7. PMID:18802065
↑ Kalatskaya I, Berchiche YA, Gravel S, Limberg BJ, Rosenbaum JS, Heveker N. AMD3100 is a CXCR7 ligand with allosteric agonist properties. Mol Pharmacol. 2009 May;75(5):1240-7. doi: 10.1124/mol.108.053389. Epub 2009 Mar , 2. PMID:19255243 doi:10.1124/mol.108.053389
↑ Veldkamp CT, Ziarek JJ, Su J, Basnet H, Lennertz R, Weiner JJ, Peterson FC, Baker JE, Volkman BF. Monomeric structure of the cardioprotective chemokine SDF-1/CXCL12. Protein Sci. 2009 Jul;18(7):1359-69. PMID:19551879 doi:10.1002/pro.167

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

Categories: Homo sapiens | Large Structures | Peterson FC | Veldkamp CT | Volkman BF

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2kec]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KEC FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kec OCA], [https://pdbe.org/2kec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kec RCSB], [https://www.ebi.ac.uk/pdbsum/2kec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kec ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2kec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kec OCA], [https://pdbe.org/2kec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kec RCSB], [https://www.ebi.ac.uk/pdbsum/2kec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kec ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ke/2kec_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>

2kec

From Proteopedia

Current revision

Structure of SDF-1/CXCL12

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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