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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<applet load="1s4y" size="450" color="white" frame="true" align="right" spinBox="true"
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caption="1s4y, resolution 2.30&Aring;" />
caption="1s4y, resolution 2.30&Aring;" />
'''Crystal structure of the activin/actrIIb extracellular domain'''<br />
'''Crystal structure of the activin/actrIIb extracellular domain'''<br />
==Overview==
==Overview==
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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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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.
==About this Structure==
==About this Structure==
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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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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://oca.weizmann.ac.il/oca-bin/ocashort?id=1S4Y OCA].
==Reference==
==Reference==
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[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: Allendorph, G.P.]]
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[[Category: Allendorph, G P.]]
[[Category: Choe, S.]]
[[Category: Choe, S.]]
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[[Category: Fischer, W.H.]]
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[[Category: Fischer, W H.]]
[[Category: Greenwald, J.]]
[[Category: Greenwald, J.]]
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[[Category: JCSG, Joint.Center.for.Structural.Genomics.]]
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[[Category: JCSG, Joint Center for Structural Genomics.]]
[[Category: Vale, W.]]
[[Category: Vale, W.]]
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[[Category: Vega, M.E.]]
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[[Category: Vega, M E.]]
[[Category: jcsg]]
[[Category: jcsg]]
[[Category: joint center for structural genomics]]
[[Category: joint center for structural genomics]]
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[[Category: transferase]]
[[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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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:58:00 2008''

Revision as of 12:58, 21 February 2008


1s4y, resolution 2.30Å

Drag the structure with the mouse to rotate

Crystal structure of the activin/actrIIb extracellular domain

Overview

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.

About this Structure

1S4Y is a Protein complex structure of sequences from Homo sapiens and Mus musculus. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.

Reference

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:15304227

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