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| - | [[Image:1mif.gif|left|200px]]<br /><applet load="1mif" size="350" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1mif, resolution 2.6Å" /> | |
| - | '''MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF)'''<br /> | |
| | | | |
| - | ==Overview== | + | ==MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF)== |
| - | Macrophage migration inhibitory factor (MIF) was the first cytokine to be described, but for 30 years its role in the immune response remained enigmatic. In recent studies, MIF has been found to be a novel pituitary hormone and the first protein identified to be released from immune cells on glucocorticoid stimulation. Once secreted, MIF counterregulates the immunosuppressive effects of steroids and thus acts as a critical component of the immune system to control both local and systemic immune responses. We report herein the x-ray crystal structure of human MIF to 2.6 angstrom resolution. The protein is a trimer of identical subunits. Each monomer contains two antiparallel alpha-helices that pack against a four-stranded beta-sheet. The monomer has an additional two beta-strands that interact with the beta-sheets of adjacent subunits to form the interface between monomers. The three beta-sheets are arranged to form a barrel containing a solvent-accessible channel that runs through the center of the protein along a molecular 3-fold axis. Electrostatic potential maps reveal that the channel has a positive potential, suggesting that it binds negatively charged molecules. The elucidated structure for MIF is unique among cytokines or hormonal mediators, and suggests that this counterregulator of glucocorticoid action participates in novel ligand-receptor interactions.
| + | <StructureSection load='1mif' size='340' side='right'caption='[[1mif]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1mif]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MIF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MIF FirstGlance]. <br> |
| | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</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=1mif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mif OCA], [https://pdbe.org/1mif PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mif RCSB], [https://www.ebi.ac.uk/pdbsum/1mif PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mif ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/MIF_HUMAN MIF_HUMAN] Genetic variations in MIF are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:[https://omim.org/entry/604302 604302]. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MIF_HUMAN MIF_HUMAN] Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity.<ref>PMID:15908412</ref> <ref>PMID:17443469</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/mi/1mif_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1mif ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | ==Disease== | + | ==See Also== |
| - | Known diseases associated with this structure: Persistent Mullerian duct syndrome, type I OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600957 600957]], Rheumatoid arthritis, systemic juvenile, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=153620 153620]]
| + | *[[Macrophage inhibitory factor 3D structures|Macrophage inhibitory factor 3D structures]] |
| - | | + | == References == |
| - | ==About this Structure== | + | <references/> |
| - | 1MIF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MIF OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference==
| + | |
| - | Crystal structure at 2.6-A resolution of human macrophage migration inhibitory factor., Sun HW, Bernhagen J, Bucala R, Lolis E, Proc Natl Acad Sci U S A. 1996 May 28;93(11):5191-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8643551 8643551]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Lolis, E.]] | + | [[Category: Lolis E]] |
| - | [[Category: Sun, H W.]] | + | [[Category: Sun H-W]] |
| - | [[Category: cytokine]]
| + | |
| - | [[Category: glutathione binding protein]]
| + | |
| - | [[Category: hormone]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:55:28 2008''
| + | |
| Structural highlights
Disease
MIF_HUMAN Genetic variations in MIF are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis.
Function
MIF_HUMAN Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Oddo M, Calandra T, Bucala R, Meylan PR. Macrophage migration inhibitory factor reduces the growth of virulent Mycobacterium tuberculosis in human macrophages. Infect Immun. 2005 Jun;73(6):3783-6. PMID:15908412 doi:10.1128/IAI.73.6.3783-3786.2005
- ↑ Emonts M, Sweep FC, Grebenchtchikov N, Geurts-Moespot A, Knaup M, Chanson AL, Erard V, Renner P, Hermans PW, Hazelzet JA, Calandra T. Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis. Clin Infect Dis. 2007 May 15;44(10):1321-8. Epub 2007 Apr 5. PMID:17443469 doi:10.1086/514344
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