2qlu: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
New page: left|200px<br /><applet load="2qlu" size="350" color="white" frame="true" align="right" spinBox="true" caption="2qlu, resolution 2.Å" /> '''Crystal structure of A...
 
No edit summary
 
(15 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2qlu.jpg|left|200px]]<br /><applet load="2qlu" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2qlu, resolution 2.&Aring;" />
'''Crystal structure of Activin receptor type II kinase domain from human'''<br />


==Overview==
==Crystal structure of Activin receptor type II kinase domain from human==
Activin receptor type IIB (ActRIIB), a type II TGF-beta serine/threonine, kinase receptor, is integral to the activin and myostatin signaling, pathway. Ligands such as activin and myostatin bind to activin type II, receptors (ActRIIA, ActRIIB), and the GS domains of type I receptors are, phosphorylated by type II receptors. Myostatin, a negative regulator of, skeletal muscle growth, is regarded as a potential therapeutic target and, binds to ActRIIB effectively, and to a lesser extent, to ActRIIA. The, high-resolution structure of human ActRIIB kinase domain in complex with, adenine establishes the conserved bilobal architecture consistent with all, other catalytic kinase domains. The crystal structure reveals that the, adenine has a considerably different orientation from that of the adenine, moiety of ATP observed in other kinase structures due to the lack of an, interaction by ribose-phosphate moiety and the presence of tautomers with, two different protonation states at the N9 nitrogen. Although the, Lys217-Glu230 salt bridge is absent, the unphosphorylated activation loop, of ActRIIB adopts a conformation similar to that of the fully active form., Unlike the type I TGF-beta receptor, where a partially conserved Ser280 is, a gatekeeper residue, the AcRIIB structure possesses Thr265 with a back, pocket supported by Phe247. Taken together, these structural features, provide a molecular basis for understanding the coupled activity and, recognition specificity for human ActRIIB kinase domain and for the, rational design of selective inhibitors.
<StructureSection load='2qlu' size='340' side='right'caption='[[2qlu]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[2qlu]] is a 1 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=2QLU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QLU FirstGlance]. <br>
2QLU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=ADE:'>ADE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QLU OCA].  
</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&#8491;</td></tr>
 
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADE:ADENINE'>ADE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qlu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qlu OCA], [https://pdbe.org/2qlu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qlu RCSB], [https://www.ebi.ac.uk/pdbsum/2qlu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qlu ProSAT]</span></td></tr>
Crystal structure of activin receptor type IIB kinase domain from human at 2.0 Angstrom resolution., Han S, Loulakis P, Griffor M, Xie Z, Protein Sci. 2007 Oct;16(10):2272-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17893364 17893364]
</table>
== Disease ==
[https://www.uniprot.org/uniprot/AVR2B_HUMAN AVR2B_HUMAN] Defects in ACVR2B are the cause of visceral heterotaxy autosomal type 4 (HTX4) [MIM:[https://omim.org/entry/613751 613751]. A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. It results in an abnormal arrangement of visceral organs, and a wide variety of congenital defects. Clinical features of visceral heterotaxy type 4 include dextrocardia, right aortic arch and a right-sided spleen, anomalies of the inferior and the superior vena cava, atrial ventricular canal defect with dextro-transposed great arteries, pulmonary stenosis, polysplenia and midline liver.<ref>PMID:9916847</ref>
== Function ==
[https://www.uniprot.org/uniprot/AVR2B_HUMAN AVR2B_HUMAN] 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.<ref>PMID:8622651</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/ql/2qlu_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=2qlu ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Receptor protein serine/threonine kinase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Han S]]
[[Category: Han, S.]]
[[Category: ADE]]
[[Category: SO4]]
[[Category: actriib]]
[[Category: alternative splicing]]
[[Category: atp-binding]]
[[Category: disease mutation]]
[[Category: glycoprotein]]
[[Category: magnesium]]
[[Category: manganese]]
[[Category: membrane]]
[[Category: metal-binding]]
[[Category: nucleotide-binding]]
[[Category: serine/threonine kinase receptor]]
[[Category: serine/threonine-protein kinase]]
[[Category: tgf-beta]]
[[Category: transferase]]
[[Category: transmembrane]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:10:06 2008''

Latest revision as of 12:16, 21 February 2024

Crystal structure of Activin receptor type II kinase domain from humanCrystal structure of Activin receptor type II kinase domain from human

Structural highlights

2qlu is a 1 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 2Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

AVR2B_HUMAN Defects in ACVR2B are the cause of visceral heterotaxy autosomal type 4 (HTX4) [MIM:613751. A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. It results in an abnormal arrangement of visceral organs, and a wide variety of congenital defects. Clinical features of visceral heterotaxy type 4 include dextrocardia, right aortic arch and a right-sided spleen, anomalies of the inferior and the superior vena cava, atrial ventricular canal defect with dextro-transposed great arteries, pulmonary stenosis, polysplenia and midline liver.[1]

Function

AVR2B_HUMAN 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.[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

  1. ↑ Kosaki R, Gebbia M, Kosaki K, Lewin M, Bowers P, Towbin JA, Casey B. Left-right axis malformations associated with mutations in ACVR2B, the gene for human activin receptor type IIB. Am J Med Genet. 1999 Jan 1;82(1):70-6. PMID:9916847
  2. ↑ Attisano L, Wrana JL, Montalvo E, Massague J. Activation of signalling by the activin receptor complex. Mol Cell Biol. 1996 Mar;16(3):1066-73. PMID:8622651

2qlu, resolution 2.00Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=2qlu&oldid=4062846"