2p6a
From Proteopedia
(New page: 200px<br /> <applet load="2p6a" size="450" color="white" frame="true" align="right" spinBox="true" caption="2p6a, resolution 3.400Å" /> '''The structure of t...) |
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| - | [[Image:2p6a. | + | [[Image:2p6a.jpg|left|200px]]<br /><applet load="2p6a" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2p6a, resolution 3.400Å" /> | caption="2p6a, resolution 3.400Å" /> | ||
'''The structure of the Activin:Follistatin 315 complex'''<br /> | '''The structure of the Activin:Follistatin 315 complex'''<br /> | ||
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==Overview== | ==Overview== | ||
Follistatin (FS) regulates transforming growth factor-beta superfamily, ligands and is necessary for normal embryonic and ovarian follicle, development. Follistatin is expressed as two splice variants (FS288 and, FS315). Previous studies indicated differences in heparin binding between, FS288 and FS315, potentially influencing the physiological functions and, locations of these isoforms. We have determined the structure of the, FS315-activin A complex and quantitatively compared heparin binding by the, two isoforms. The FS315 complex structure shows that both isoforms inhibit, activin similarly, but FS315 exhibits movements within follistatin domain, 3 (FSD3) apparently linked to binding of the C-terminal extension., Surprisingly, the binding affinities of FS288 and FS315 for heparin are, similar at lower ionic strengths with FS315 binding decreasing more, sharply as a function of salt concentration. When bound to activin, FS315, binds heparin similarly to the FS288 isoform, consistent with the, structure of the complex, in which the acidic residues of the C-terminal, extension cannot interact with the heparin-binding site. Activin-induced, binding of heparin is unique to the FS315 isoform and may stimulate, clearance of FS315 complexes. | Follistatin (FS) regulates transforming growth factor-beta superfamily, ligands and is necessary for normal embryonic and ovarian follicle, development. Follistatin is expressed as two splice variants (FS288 and, FS315). Previous studies indicated differences in heparin binding between, FS288 and FS315, potentially influencing the physiological functions and, locations of these isoforms. We have determined the structure of the, FS315-activin A complex and quantitatively compared heparin binding by the, two isoforms. The FS315 complex structure shows that both isoforms inhibit, activin similarly, but FS315 exhibits movements within follistatin domain, 3 (FSD3) apparently linked to binding of the C-terminal extension., Surprisingly, the binding affinities of FS288 and FS315 for heparin are, similar at lower ionic strengths with FS315 binding decreasing more, sharply as a function of salt concentration. When bound to activin, FS315, binds heparin similarly to the FS288 isoform, consistent with the, structure of the complex, in which the acidic residues of the C-terminal, extension cannot interact with the heparin-binding site. Activin-induced, binding of heparin is unique to the FS315 isoform and may stimulate, clearance of FS315 complexes. | ||
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| - | ==Disease== | ||
| - | Known disease associated with this structure: Polycystic ovary syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=136470 136470]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2P6A is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2P6A is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=2P6A OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tgf-beta]] | [[Category: tgf-beta]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:59:33 2008'' |
Revision as of 12:59, 23 January 2008
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The structure of the Activin:Follistatin 315 complex
Overview
Follistatin (FS) regulates transforming growth factor-beta superfamily, ligands and is necessary for normal embryonic and ovarian follicle, development. Follistatin is expressed as two splice variants (FS288 and, FS315). Previous studies indicated differences in heparin binding between, FS288 and FS315, potentially influencing the physiological functions and, locations of these isoforms. We have determined the structure of the, FS315-activin A complex and quantitatively compared heparin binding by the, two isoforms. The FS315 complex structure shows that both isoforms inhibit, activin similarly, but FS315 exhibits movements within follistatin domain, 3 (FSD3) apparently linked to binding of the C-terminal extension., Surprisingly, the binding affinities of FS288 and FS315 for heparin are, similar at lower ionic strengths with FS315 binding decreasing more, sharply as a function of salt concentration. When bound to activin, FS315, binds heparin similarly to the FS288 isoform, consistent with the, structure of the complex, in which the acidic residues of the C-terminal, extension cannot interact with the heparin-binding site. Activin-induced, binding of heparin is unique to the FS315 isoform and may stimulate, clearance of FS315 complexes.
About this Structure
2P6A is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural and biophysical coupling of heparin and activin binding to follistatin isoform functions., Lerch TF, Shimasaki S, Woodruff TK, Jardetzky TS, J Biol Chem. 2007 May 25;282(21):15930-9. Epub 2007 Apr 3. PMID:17409095
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