1s4y

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(New page: 200px<br /> <applet load="1s4y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s4y, resolution 2.30&Aring;" /> '''Crystal structure o...)
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[[Image:1s4y.gif|left|200px]]<br />
 
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<applet load="1s4y" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1s4y, resolution 2.30&Aring;" />
 
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'''Crystal structure of the activin/actrIIb extracellular domain'''<br />
 
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==Overview==
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==Crystal structure of the activin/actrIIb extracellular domain==
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A new crystal structure of activin in complex with the extracellular, domain of its type II receptor (ActRIIb-ECD) shows that the ligand, exhibits an unexpected flexibility. The motion in the activin dimer, disrupts its type I receptor interface, which may account for the, disparity in its affinity for type I versus type II receptors. We have, measured the affinities of activin and its antagonist inhibin for, ActRIIb-ECD and found that the affinity of the 2-fold symmetric homodimer, activin for ActRIIb-ECD depends on the availability of two spatially, coupled ActRIIb-ECD molecules, whereas the affinity of the heterodimer, inhibin does not. Our results indicate that activin's affinity for its two, receptor types is greatly influenced by their membrane-restricted setting., We propose that activin affinity is modulated by the ligand flexibility, and that cooperativity is achieved by binding to two ActRII chains that, immobilize activin in a type I binding-competent orientation.
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<StructureSection load='1s4y' size='340' side='right'caption='[[1s4y]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1s4y]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S4Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S4Y FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1s4y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s4y OCA], [https://pdbe.org/1s4y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s4y RCSB], [https://www.ebi.ac.uk/pdbsum/1s4y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s4y ProSAT], [https://www.topsan.org/Proteins/JCSG/1s4y TOPSAN]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/AVR2B_MOUSE AVR2B_MOUSE] Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, the type-2 receptors act as a primary activin receptors (binds activin-A/INHBA, activin-B/INHBB as well as inhibin-A/INHA-INHBA). The type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/s4/1s4y_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=1s4y ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1S4Y is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S4Y OCA].
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*[[Activin|Activin]]
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__TOC__
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==Reference==
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</StructureSection>
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A flexible activin explains the membrane-dependent cooperative assembly of TGF-beta family receptors., Greenwald J, Vega ME, Allendorph GP, Fischer WH, Vale W, Choe S, Mol Cell. 2004 Aug 13;15(3):485-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15304227 15304227]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Allendorph GP]]
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[[Category: Protein complex]]
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[[Category: Choe S]]
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[[Category: Allendorph, G.P.]]
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[[Category: Fischer WH]]
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[[Category: Choe, S.]]
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[[Category: Greenwald J]]
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[[Category: Fischer, W.H.]]
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[[Category: Vale W]]
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[[Category: Greenwald, J.]]
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[[Category: Vega ME]]
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[[Category: JCSG, Joint.Center.for.Structural.Genomics.]]
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[[Category: Vale, W.]]
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[[Category: Vega, M.E.]]
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[[Category: jcsg]]
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[[Category: joint center for structural genomics]]
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[[Category: protein structure initiative]]
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[[Category: psi]]
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[[Category: structural genomics]]
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[[Category: transferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:10:36 2007''
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Current revision

Crystal structure of the activin/actrIIb extracellular domain

PDB ID 1s4y

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