2ibb
From Proteopedia
(New page: 200px<br /><applet load="2ibb" size="350" color="white" frame="true" align="right" spinBox="true" caption="2ibb, resolution 2.400Å" /> '''Crystal Structure o...) |
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==Overview== | ==Overview== | ||
| - | Hedgehog (Hh) signaling molecules mediate key tissue-patterning events | + | Hedgehog (Hh) signaling molecules mediate key tissue-patterning events during animal development, and inappropriate activation of Hh signaling in adults has been associated with human cancers. Recently, a conserved family of type I integral membrane proteins required for normal response to the Hh signal was discovered. One member of this family, Ihog (interference hedgehog), functions upstream or at the level of Patched (Ptc), but how Ihog participates in Hh signaling remains unclear. Here, we show that heparin binding induces Ihog dimerization and is required to mediate high-affinity interactions between Ihog and Hh. We also present crystal structures of a Hh-binding fragment of Ihog, both alone and complexed with Hh. Heparin is not well ordered in these structures, but a basic cleft in the first FNIII domain of Ihog (IhogFn1) is shown by mutagenesis to mediate heparin binding. These results establish that Hh directly binds Ihog and provide the first demonstration of a specific role for heparin in Hh responsiveness. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Drosophila melanogaster]] | [[Category: Drosophila melanogaster]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Leahy, D | + | [[Category: Leahy, D J.]] |
| - | [[Category: McLellan, J | + | [[Category: McLellan, J S.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: fibronectin type iii]] | [[Category: fibronectin type iii]] | ||
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[[Category: ihog]] | [[Category: ihog]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:51:01 2008'' |
Revision as of 15:51, 21 February 2008
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Crystal Structure of the First and Second FNIII Domains of Ihog
Overview
Hedgehog (Hh) signaling molecules mediate key tissue-patterning events during animal development, and inappropriate activation of Hh signaling in adults has been associated with human cancers. Recently, a conserved family of type I integral membrane proteins required for normal response to the Hh signal was discovered. One member of this family, Ihog (interference hedgehog), functions upstream or at the level of Patched (Ptc), but how Ihog participates in Hh signaling remains unclear. Here, we show that heparin binding induces Ihog dimerization and is required to mediate high-affinity interactions between Ihog and Hh. We also present crystal structures of a Hh-binding fragment of Ihog, both alone and complexed with Hh. Heparin is not well ordered in these structures, but a basic cleft in the first FNIII domain of Ihog (IhogFn1) is shown by mutagenesis to mediate heparin binding. These results establish that Hh directly binds Ihog and provide the first demonstration of a specific role for heparin in Hh responsiveness.
About this Structure
2IBB is a Single protein structure of sequence from Drosophila melanogaster with as ligand. Full crystallographic information is available from OCA.
Reference
Structure of a heparin-dependent complex of Hedgehog and Ihog., McLellan JS, Yao S, Zheng X, Geisbrecht BV, Ghirlando R, Beachy PA, Leahy DJ, Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17208-13. Epub 2006 Oct 31. PMID:17077139
Page seeded by OCA on Thu Feb 21 17:51:01 2008
