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3b4v

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Revision as of 07:55, 25 October 2017

X-Ray structure of Activin in complex with FSTL3

Structural highlights

3b4v is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	INHBA (HUMAN), FSTL3, FLRG (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[FSTL3_HUMAN] Note=A chromosomal aberration involving FSTL3 is found in a case of B-cell chronic lymphocytic leukemia. Translocation t(11;19)(q13;p13) with CCDN1.

Function

[INHBA_HUMAN] Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins. [FSTL3_HUMAN] Isoform 1 or the secreted form is a binding and antagonizing protein for members of the TGF-beta family, such us activin, BMP2 and MSTN. Inhibits activin A-, activin B-, BMP2- and MSDT-induced cellular signaling; more effective on activin A than on activin B. Involved in bone formation; inhibits osteoclast differentiationc. Involved in hematopoiesis; involved in differentiation of hemopoietic progenitor cells, increases hematopoietic cell adhesion to fibronectin and seems to contribute to the adhesion of hematopoietic precursor cells to the bone marrow stroma. Isoform 2 or the nuclear form is probably involved in transcriptional regulation via interaction with MLLT10.^[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

Transforming growth factor beta family ligands are neutralized by a number of structurally divergent antagonists. Follistatin-type antagonists, which include splice variants of follistatin (FS288 and FS315) and follistatin-like 3 (FSTL3), have high affinity for activin A but differ in their affinity for other ligands, particularly bone morphogenetic proteins. To understand the structural basis for ligand specificity within FS-type antagonists, we determined the x-ray structure of activin A in complex with FSTL3 to a resolution of 2.5 A. Similar to the previously resolved FS.activin A structures, the ligand is encircled by two antagonist molecules blocking all ligand receptor-binding sites. Recently, the significance of the FS N-terminal domain interaction at the ligand type I receptor site has been questioned; however, our data show that for FSTL3, the N-terminal domain forms a more intimate contact with activin A, implying that this interaction is stronger than that for FS. Furthermore, binding studies revealed that replacing the FSTL3 N-terminal domain with the corresponding FS domain considerably lowers activin A affinity. Therefore, both structural and biochemical evidence support a significant interaction of the N-terminal domain of FSTL3 with activin A. In addition, structural comparisons with bone morphogenetic proteins suggest that the interface where the N-terminal domain binds may be the key site for determining FS-type antagonist specificity.

The structure of FSTL3.activin A complex. Differential binding of N-terminal domains influences follistatin-type antagonist specificity.,Stamler R, Keutmann HT, Sidis Y, Kattamuri C, Schneyer A, Thompson TB J Biol Chem. 2008 Nov 21;283(47):32831-8. Epub 2008 Sep 2. PMID:18768470^[7]

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

References

↑ Bartholin L, Maguer-Satta V, Hayette S, Martel S, Gadoux M, Corbo L, Magaud JP, Rimokh R. Transcription activation of FLRG and follistatin by activin A, through Smad proteins, participates in a negative feedback loop to modulate activin A function. Oncogene. 2002 Mar 28;21(14):2227-35. PMID:11948405 doi:10.1038/sj.onc.1205294
↑ Maguer-Satta V, Rimokh R. FLRG, member of the follistatin family, a new player in hematopoiesis. Mol Cell Endocrinol. 2004 Oct 15;225(1-2):109-18. PMID:15451575 doi:10.1016/j.mce.2004.07.009
↑ Bartholin L, Destaing O, Forissier S, Martel S, Maguer-Satta V, Jurdic P, Rimokh R. FLRG, a new ADAM12-associated protein, modulates osteoclast differentiation. Biol Cell. 2005 Jul;97(7):577-88. PMID:15574124 doi:10.1042/BC20040506
↑ Maguer-Satta V, Forissier S, Bartholin L, Martel S, Jeanpierre S, Bachelard E, Rimokh R. A novel role for fibronectin type I domain in the regulation of human hematopoietic cell adhesiveness through binding to follistatin domains of FLRG and follistatin. Exp Cell Res. 2006 Feb 15;312(4):434-42. Epub 2005 Dec 5. PMID:16336961 doi:10.1016/j.yexcr.2005.11.006
↑ Forissier S, Razanajaona D, Ay AS, Martel S, Bartholin L, Rimokh R. AF10-dependent transcription is enhanced by its interaction with FLRG. Biol Cell. 2007 Oct;99(10):563-71. PMID:17868029
↑ Takehara-Kasamatsu Y, Tsuchida K, Nakatani M, Murakami T, Kurisaki A, Hashimoto O, Ohuchi H, Kurose H, Mori K, Kagami S, Noji S, Sugino H. Characterization of follistatin-related gene as a negative regulatory factor for activin family members during mouse heart development. J Med Invest. 2007 Aug;54(3-4):276-88. PMID:17878677
↑ Stamler R, Keutmann HT, Sidis Y, Kattamuri C, Schneyer A, Thompson TB. The structure of FSTL3.activin A complex. Differential binding of N-terminal domains influences follistatin-type antagonist specificity. J Biol Chem. 2008 Nov 21;283(47):32831-8. Epub 2008 Sep 2. PMID:18768470 doi:10.1074/jbc.M801266200

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3b4v"

@@ Line 1: / Line 1: @@
 ==X-Ray structure of Activin in complex with FSTL3==
 <StructureSection load='3b4v' size='340' side='right' caption='[[3b4v]], [[Resolution|resolution]] 2.48&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">INHBA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), FSTL3, FLRG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3b4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b4v OCA], [http://pdbe.org/3b4v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3b4v RCSB], [http://www.ebi.ac.uk/pdbsum/3b4v PDBsum]</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=3b4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b4v OCA], [http://pdbe.org/3b4v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3b4v RCSB], [http://www.ebi.ac.uk/pdbsum/3b4v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3b4v ProSAT]</span></td></tr>
 </table>
 == Disease ==

3b4v

From Proteopedia

Revision as of 07:55, 25 October 2017

X-Ray structure of Activin in complex with FSTL3

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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