4dke: Difference between revisions

Latest revision as of 06:54, 27 November 2024

Crystal Structure of Human Interleukin-34 Bound to FAb1.1

Structural highlights

4dke is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Ligands:	BMA, MAN, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IL34_HUMAN Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Lacking any discernible sequence similarity, interleukin-34 (IL-34) and colony stimulating factor 1 (CSF-1) signal through a common receptor CSF-1R on cells of mononuclear phagocyte lineage. Here, the crystal structure of dimeric IL-34 reveals a helical cytokine fold homologous to CSF-1, and we further show that the complex architecture of IL-34 bound to the N-terminal immunoglobulin domains of CSF-1R is similar to the CSF-1/CSF-1R assembly. However, unique conformational adaptations in the receptor domain geometry and intermolecular interface explain the cross-reactivity of CSF-1R for two such distantly related ligands. The docking adaptations of the IL-34 and CSF-1 quaternary complexes, when compared to the stem cell factor assembly, draw a common evolutionary theme for transmembrane signaling. In addition, the structure of IL-34 engaged by a Fab fragment reveals the mechanism of a neutralizing antibody that can help deconvolute IL-34 from CSF-1 biology, with implications for therapeutic intervention in diseases with myeloid pathogenic mechanisms.

Structural Basis for the Dual Recognition of Helical Cytokines IL-34 and CSF-1 by CSF-1R.,Ma X, Lin WY, Chen Y, Stawicki S, Mukhyala K, Wu Y, Martin F, Bazan JF, Starovasnik MA Structure. 2012 Apr 4;20(4):676-87. Epub 2012 Apr 3. PMID:22483114^[5]

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

References

↑ Lin H, Lee E, Hestir K, Leo C, Huang M, Bosch E, Halenbeck R, Wu G, Zhou A, Behrens D, Hollenbaugh D, Linnemann T, Qin M, Wong J, Chu K, Doberstein SK, Williams LT. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science. 2008 May 9;320(5877):807-11. doi: 10.1126/science.1154370. PMID:18467591 doi:10.1126/science.1154370
↑ Chihara T, Suzu S, Hassan R, Chutiwitoonchai N, Hiyoshi M, Motoyoshi K, Kimura F, Okada S. IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation. Cell Death Differ. 2010 Dec;17(12):1917-27. doi: 10.1038/cdd.2010.60. Epub 2010, May 21. PMID:20489731 doi:10.1038/cdd.2010.60
↑ Eda H, Zhang J, Keith RH, Michener M, Beidler DR, Monahan JB. Macrophage-colony stimulating factor and interleukin-34 induce chemokines in human whole blood. Cytokine. 2010 Dec;52(3):215-20. doi: 10.1016/j.cyto.2010.08.005. Epub 2010 Sep, 9. PMID:20829061 doi:10.1016/j.cyto.2010.08.005
↑ Wei S, Nandi S, Chitu V, Yeung YG, Yu W, Huang M, Williams LT, Lin H, Stanley ER. Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells. J Leukoc Biol. 2010 Sep;88(3):495-505. doi: 10.1189/jlb.1209822. Epub 2010 May, 26. PMID:20504948 doi:10.1189/jlb.1209822
↑ Ma X, Lin WY, Chen Y, Stawicki S, Mukhyala K, Wu Y, Martin F, Bazan JF, Starovasnik MA. Structural Basis for the Dual Recognition of Helical Cytokines IL-34 and CSF-1 by CSF-1R. Structure. 2012 Apr 4;20(4):676-87. Epub 2012 Apr 3. PMID:22483114 doi:10.1016/j.str.2012.02.010

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Lin H, Lee E, Hestir K, Leo C, Huang M, Bosch E, Halenbeck R, Wu G, Zhou A, Behrens D, Hollenbaugh D, Linnemann T, Qin M, Wong J, Chu K, Doberstein SK, Williams LT. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science. 2008 May 9;320(5877):807-11. doi: 10.1126/science.1154370. PMID:18467591 doi:10.1126/science.1154370

[2] Chihara T, Suzu S, Hassan R, Chutiwitoonchai N, Hiyoshi M, Motoyoshi K, Kimura F, Okada S. IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation. Cell Death Differ. 2010 Dec;17(12):1917-27. doi: 10.1038/cdd.2010.60. Epub 2010, May 21. PMID:20489731 doi:10.1038/cdd.2010.60

[3] Eda H, Zhang J, Keith RH, Michener M, Beidler DR, Monahan JB. Macrophage-colony stimulating factor and interleukin-34 induce chemokines in human whole blood. Cytokine. 2010 Dec;52(3):215-20. doi: 10.1016/j.cyto.2010.08.005. Epub 2010 Sep, 9. PMID:20829061 doi:10.1016/j.cyto.2010.08.005

[4] Wei S, Nandi S, Chitu V, Yeung YG, Yu W, Huang M, Williams LT, Lin H, Stanley ER. Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells. J Leukoc Biol. 2010 Sep;88(3):495-505. doi: 10.1189/jlb.1209822. Epub 2010 May, 26. PMID:20504948 doi:10.1189/jlb.1209822

[5] Ma X, Lin WY, Chen Y, Stawicki S, Mukhyala K, Wu Y, Martin F, Bazan JF, Starovasnik MA. Structural Basis for the Dual Recognition of Helical Cytokines IL-34 and CSF-1 by CSF-1R. Structure. 2012 Apr 4;20(4):676-87. Epub 2012 Apr 3. PMID:22483114 doi:10.1016/j.str.2012.02.010

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Human Interleukin-34 Bound to FAb1.1==
-<StructureSection load='4dke' size='340' side='right' caption='[[4dke]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+<StructureSection load='4dke' size='340' side='right'caption='[[4dke]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4dke]] is a 6 chain structure with 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=4DKE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DKE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4dke]] is a 6 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=4DKE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DKE FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dkc|4dkc]], [[4dkd|4dkd]], [[4dkf|4dkf]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL34, C16orf77 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4dke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dke OCA], [https://pdbe.org/4dke PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dke RCSB], [https://www.ebi.ac.uk/pdbsum/4dke PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dke ProSAT]</span></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=4dke FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dke OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dke RCSB], [http://www.ebi.ac.uk/pdbsum/4dke PDBsum]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/IL34_HUMAN IL34_HUMAN] Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.<ref>PMID:18467591</ref> <ref>PMID:20489731</ref> <ref>PMID:20829061</ref> <ref>PMID:20504948</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 16: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4dke" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Interleukin|Interleukin]]
+*[[Interleukin 3D structures|Interleukin 3D structures]]
 == References ==
 <references/>
@@ Line 24: / Line 27: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Bazan, J F]]
+[[Category: Large Structures]]
-[[Category: Chen, Y]]
+[[Category: Bazan JF]]
-[[Category: Ma, X]]
+[[Category: Chen Y]]
-[[Category: Starovasnik, M A]]
+[[Category: Ma X]]
-[[Category: Stawicki, S]]
+[[Category: Starovasnik MA]]
-[[Category: Wu, Y]]
+[[Category: Stawicki S]]
-[[Category: Cytokine-immune system complex]]
+[[Category: Wu Y]]
-[[Category: Dimeric four-helix bundle cytokine]]
-[[Category: Glycosylation]]
-[[Category: Igg]]

4dke: Difference between revisions

Latest revision as of 06:54, 27 November 2024

Crystal Structure of Human Interleukin-34 Bound to FAb1.1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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