1m1l
From Proteopedia
(New page: 200px<br /> <applet load="1m1l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m1l, resolution 2.65Å" /> '''Human Suppressor of...) |
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| - | [[Image:1m1l.gif|left|200px]]<br /> | + | [[Image:1m1l.gif|left|200px]]<br /><applet load="1m1l" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1m1l" size=" | + | |
caption="1m1l, resolution 2.65Å" /> | caption="1m1l, resolution 2.65Å" /> | ||
'''Human Suppressor of Fused (N-terminal domain)'''<br /> | '''Human Suppressor of Fused (N-terminal domain)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Hedgehog pathway drives proliferation and differentiation by | + | The Hedgehog pathway drives proliferation and differentiation by activating the Gli/Ci family of zinc finger transcription factors. Gli/Ci proteins form Hedgehog signaling complexes with other signaling components, including the kinesin-like protein Costal-2, the serine-threonine kinase Fused, and Suppressor of Fused [Su(fu)]. In these complexes Gli/Ci proteins are regulated by cytoplasmic sequestration, phosphorylation, and proteolysis. Here we characterize structural and functional determinants of Su(fu) required for Gli regulation and show that Su(fu) contains at least two distinct domains: a highly conserved carboxy-terminal region required for binding to the amino-terminal ends of the Gli proteins and a unique amino-terminal domain that binds the carboxy-terminal tail of Gli1. While each domain is capable of binding to different Gli1 regions independently, interactions between Su(fu) and Gli1 at both sites are required for cytoplasmic tethering and repression of Gli1. Furthermore, we have solved the crystal structure of the amino-terminal domain of human Su(fu)(27-268) at 2.65 A resolution. This domain forms a concave pocket with a prominent acidic patch. Mutation at Asp(159) in the acidic patch disrupts Gli1 tethering and repression while not strongly disrupting binding, indicating that the amino-terminal domain of Su(fu) likely impacts Gli binding through a mechanism distinct from that for tethering and repression. These studies provide a structural basis for understanding the function of Su(fu). |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1M1L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1M1L is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=1M1L OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Cannon, J.]] | [[Category: Cannon, J.]] | ||
| - | [[Category: Lazarus, R | + | [[Category: Lazarus, R A.]] |
| - | [[Category: Maun, H | + | [[Category: Maun, H R.]] |
[[Category: Merchant, M.]] | [[Category: Merchant, M.]] | ||
| - | [[Category: Sauvage, F | + | [[Category: Sauvage, F J.de.]] |
[[Category: Ultsch, M.]] | [[Category: Ultsch, M.]] | ||
| - | [[Category: Vajdos, F | + | [[Category: Vajdos, F F.]] |
| - | [[Category: Vos, A | + | [[Category: Vos, A M.de.]] |
[[Category: Wendt, U.]] | [[Category: Wendt, U.]] | ||
[[Category: fused]] | [[Category: fused]] | ||
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[[Category: signal transduction]] | [[Category: signal transduction]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:50:31 2008'' |
Revision as of 11:50, 21 February 2008
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Human Suppressor of Fused (N-terminal domain)
Contents |
Overview
The Hedgehog pathway drives proliferation and differentiation by activating the Gli/Ci family of zinc finger transcription factors. Gli/Ci proteins form Hedgehog signaling complexes with other signaling components, including the kinesin-like protein Costal-2, the serine-threonine kinase Fused, and Suppressor of Fused [Su(fu)]. In these complexes Gli/Ci proteins are regulated by cytoplasmic sequestration, phosphorylation, and proteolysis. Here we characterize structural and functional determinants of Su(fu) required for Gli regulation and show that Su(fu) contains at least two distinct domains: a highly conserved carboxy-terminal region required for binding to the amino-terminal ends of the Gli proteins and a unique amino-terminal domain that binds the carboxy-terminal tail of Gli1. While each domain is capable of binding to different Gli1 regions independently, interactions between Su(fu) and Gli1 at both sites are required for cytoplasmic tethering and repression of Gli1. Furthermore, we have solved the crystal structure of the amino-terminal domain of human Su(fu)(27-268) at 2.65 A resolution. This domain forms a concave pocket with a prominent acidic patch. Mutation at Asp(159) in the acidic patch disrupts Gli1 tethering and repression while not strongly disrupting binding, indicating that the amino-terminal domain of Su(fu) likely impacts Gli binding through a mechanism distinct from that for tethering and repression. These studies provide a structural basis for understanding the function of Su(fu).
Disease
Known disease associated with this structure: Medulloblastoma, desmoplastic OMIM:[607035]
About this Structure
1M1L is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Suppressor of fused regulates Gli activity through a dual binding mechanism., Merchant M, Vajdos FF, Ultsch M, Maun HR, Wendt U, Cannon J, Desmarais W, Lazarus RA, de Vos AM, de Sauvage FJ, Mol Cell Biol. 2004 Oct;24(19):8627-41. PMID:15367681
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