View source for 2kee


==Structure of SDF-1/CXCL12==
<StructureSection load='2kee' size='340' side='right'caption='[[2kee]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2kee]] 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=2KEE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KEE FirstGlance]. <br>
</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=2kee FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kee OCA], [https://pdbe.org/2kee PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kee RCSB], [https://www.ebi.ac.uk/pdbsum/2kee PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kee ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SDF1_HUMAN 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.<ref>PMID:8752281</ref> <ref>PMID:11069075</ref> <ref>PMID:11859124</ref> <ref>PMID:16107333</ref> <ref>PMID:18802065</ref> <ref>PMID:19255243</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ke/2kee_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kee ConSurf].
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== 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<ref>PMID:19551879</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2kee" style="background-color:#fffaf0;"></div>

==See Also==
*[[C-X-C motif chemokine 3D structures|C-X-C motif chemokine 3D structures]]
*[[Stromal Derived Factor 1|Stromal Derived Factor 1]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Peterson FC]]
[[Category: Veldkamp CT]]
[[Category: Volkman BF]]