2aze
From Proteopedia
(New page: 200px<br /> <applet load="2aze" size="450" color="white" frame="true" align="right" spinBox="true" caption="2aze, resolution 2.55Å" /> '''Structure of the Rb...) |
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| - | [[Image:2aze.gif|left|200px]]<br /> | + | [[Image:2aze.gif|left|200px]]<br /><applet load="2aze" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2aze" size=" | + | |
caption="2aze, resolution 2.55Å" /> | caption="2aze, resolution 2.55Å" /> | ||
'''Structure of the Rb C-terminal domain bound to an E2F1-DP1 heterodimer'''<br /> | '''Structure of the Rb C-terminal domain bound to an E2F1-DP1 heterodimer'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The retinoblastoma (Rb) protein negatively regulates the G1-S transition | + | The retinoblastoma (Rb) protein negatively regulates the G1-S transition by binding to the E2F transcription factors, until cyclin-dependent kinases phosphorylate Rb, causing E2F release. The Rb pocket domain is necessary for E2F binding, but the Rb C-terminal domain (RbC) is also required for growth suppression. Here we demonstrate a high-affinity interaction between RbC and E2F-DP heterodimers shared by all Rb and E2F family members. The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC. We also demonstrate that phosphorylation of RbC at serines 788 and 795 destabilizes one set of RbC-E2F-DP interactions directly, while phosphorylation at threonines 821 and 826 induces an intramolecular interaction between RbC and the Rb pocket that destabilizes the remaining interactions indirectly. Our findings explain the requirement of RbC for high-affinity E2F binding and growth suppression and establish a mechanism for the regulation of Rb-E2F association by phosphorylation. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2AZE 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:// | + | 2AZE 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=2AZE OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Gall, A | + | [[Category: Gall, A L.]] |
| - | [[Category: Pavletich, N | + | [[Category: Pavletich, N P.]] |
| - | [[Category: Rubin, S | + | [[Category: Rubin, S M.]] |
[[Category: Zheng, N.]] | [[Category: Zheng, N.]] | ||
[[Category: beta sandwich]] | [[Category: beta sandwich]] | ||
[[Category: coiled coil]] | [[Category: coiled coil]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:32:37 2008'' |
Revision as of 14:32, 21 February 2008
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Structure of the Rb C-terminal domain bound to an E2F1-DP1 heterodimer
Contents |
Overview
The retinoblastoma (Rb) protein negatively regulates the G1-S transition by binding to the E2F transcription factors, until cyclin-dependent kinases phosphorylate Rb, causing E2F release. The Rb pocket domain is necessary for E2F binding, but the Rb C-terminal domain (RbC) is also required for growth suppression. Here we demonstrate a high-affinity interaction between RbC and E2F-DP heterodimers shared by all Rb and E2F family members. The crystal structure of an RbC-E2F1-DP1 complex reveals an intertwined heterodimer in which the marked box domains of both E2F1 and DP1 contact RbC. We also demonstrate that phosphorylation of RbC at serines 788 and 795 destabilizes one set of RbC-E2F-DP interactions directly, while phosphorylation at threonines 821 and 826 induces an intramolecular interaction between RbC and the Rb pocket that destabilizes the remaining interactions indirectly. Our findings explain the requirement of RbC for high-affinity E2F binding and growth suppression and establish a mechanism for the regulation of Rb-E2F association by phosphorylation.
Disease
Known diseases associated with this structure: Bladder cancer OMIM:[180200], Osteosarcoma OMIM:[180200], Pinealoma with bilateral retinoblastoma OMIM:[180200], Retinoblastoma OMIM:[180200]
About this Structure
2AZE is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release., Rubin SM, Gall AL, Zheng N, Pavletich NP, Cell. 2005 Dec 16;123(6):1093-106. PMID:16360038
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