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| ==HUMAN INTERLEUKIN 3 (IL-3) MUTANT WITH TRUNCATION AT BOTH N-AND C-TERMINI AND 14 RESIDUE CHANGES, NMR, MINIMIZED AVERAGE STRUCTURE== | | ==HUMAN INTERLEUKIN 3 (IL-3) MUTANT WITH TRUNCATION AT BOTH N-AND C-TERMINI AND 14 RESIDUE CHANGES, NMR, MINIMIZED AVERAGE STRUCTURE== |
| <StructureSection load='1jli' size='340' side='right'caption='[[1jli]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | | <StructureSection load='1jli' size='340' side='right'caption='[[1jli]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1jli]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JLI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JLI FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1jli]] 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=1JLI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JLI 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=1jli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jli OCA], [https://pdbe.org/1jli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jli RCSB], [https://www.ebi.ac.uk/pdbsum/1jli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jli 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</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=1jli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jli OCA], [https://pdbe.org/1jli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jli RCSB], [https://www.ebi.ac.uk/pdbsum/1jli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jli ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
| [[https://www.uniprot.org/uniprot/IL3_HUMAN IL3_HUMAN]] Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This CSF induces granulocytes, macrophages, mast cells, stem cells, erythroid cells, eosinophils and megakaryocytes.
| | [https://www.uniprot.org/uniprot/IL3_HUMAN IL3_HUMAN] Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This CSF induces granulocytes, macrophages, mast cells, stem cells, erythroid cells, eosinophils and megakaryocytes. |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| </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=1jli ConSurf]. | | </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=1jli ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The three-dimensional structure and backbone dynamics of a truncated and multiply substituted recombinant human interleukin-3 (IL-3) variant (SC-65369) have been determined from multidimensional heteronuclear nuclear magnetic resonance spectroscopic data. Sequential application of distance geometry and restrained molecular dynamics calculations produced a family of 25 convergent structures which satisfy a total of 1812 experimental constraints (1659 proton-proton NOEs, 75 backbone dihedral angle constraints, and 39 pairs of hydrogen bond constraints) with an average root-mean-square deviation from the mean coordinate positions of 0.88(+/- 0.15) angstroms and 1.37(+/- 0.13) angstroms for the backbone and all heavy atoms, respectively, of all residues except 28 to 39. The structure is a left-handed four-helix bundle (comprised of helices A through D) with two long overhand loops (designated as loops AB and CD). Loop AB contains a short fifth helix (helix A') which is closely packed against helix D in an approximately parallel fashion and which has multiple contacts with loop CD. The overall molecular tumbling time (6.5 ns) determined from the 15N relaxation data was consistent with a monomeric protein under the conditions of the experiment (1 mM protein, pH 4.6, 30 degrees C). The 15N relaxation data indicate that the helical regions of SC-65369 are quite rigid, while portions of loop AB, loop CD, and the C terminus undergo significant internal motions. Among the structurally related four-helical bundle cytokines, the structure of SC-65369 is most similar to those of granulocyte-macrophage colony stimulating factor (GM-CSF) and the single structural domain of interleukin-5 (IL-5), all of which share a common receptor subunit required for signal transduction and activation of their hematopoietic target cells. Indeed, the C(alpha) atoms in the four-helix core of these three proteins can be superimposed to 1.71 angstroms (SC-65369 and GM-CSF, 62 C(alpha) atoms) and 1.96 angstroms (SC-65369 and IL-5 single structural domain, 58 C(alpha) atoms), respectively. When the structures of the IL-3 variant, GM-CSF, and IL-5 were aligned, the conserved and conservatively substituted residues were found to be hydrophobic and buried, with the single exception of Glu-22 (IL-3 numbering), which is strictly conserved but nonetheless fully exposed to solvent. The most remarkable differences between the SC-65369 structure and that of GM-CSF occur in loop AB. This loop in GM-CSF crosses over the top of helix D and passes underneath loop CD on its way to helix B. In contrast, loop AB of SC-65369 passes in front of helix D, similar to the first crossover loop in human growth hormone and granulocyte colony-stimulating factor. In addition, helix A', which is interdigitated into the helical bundle in a manner similar to the helices in the CD loop of interferon-beta and interferon-gamma, exists in a region where short stretches of beta-structure are found at analogous positions in GM-CSF and IL-5. These differences suggest that the structural elements within this region may be important for recognition by their cognate receptors.
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| Three-dimensional solution structure and backbone dynamics of a variant of human interleukin-3.,Feng Y, Klein BK, McWherter CA J Mol Biol. 1996 Jun 14;259(3):524-41. PMID:8676386<ref>PMID:8676386</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 1jli" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Interleukin 3D structures|Interleukin 3D structures]] | | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Feng, Y]] | | [[Category: Feng Y]] |
| [[Category: Klein, B K]] | | [[Category: Klein BK]] |
| [[Category: Mcwherter, C A]] | | [[Category: Mcwherter CA]] |
| [[Category: Colony-stimulating factor]]
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| [[Category: Cytokine]]
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| [[Category: Hematopoietic growth factor]]
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