2ak5
From Proteopedia
(New page: 200px<br /> <applet load="2ak5" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ak5, resolution 1.85Å" /> '''beta PIX-SH3 comple...) |
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| - | [[Image:2ak5.gif|left|200px]]<br /> | + | [[Image:2ak5.gif|left|200px]]<br /><applet load="2ak5" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2ak5" size=" | + | |
caption="2ak5, resolution 1.85Å" /> | caption="2ak5, resolution 1.85Å" /> | ||
'''beta PIX-SH3 complexed with a Cbl-b peptide'''<br /> | '''beta PIX-SH3 complexed with a Cbl-b peptide'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The ubiquitin ligases c-Cbl and Cbl-b play a crucial role in receptor | + | The ubiquitin ligases c-Cbl and Cbl-b play a crucial role in receptor downregulation by mediating multiple monoubiquitination of receptors and promoting their sorting for lysosomal degradation. Their function is modulated through interactions with regulatory proteins including CIN85 and PIX, which recognize a proline-arginine motif in Cbl and thus promote or inhibit receptor endocytosis. We report the structures of SH3 domains of CIN85 and beta-PIX in complex with a proline-arginine peptide from Cbl-b. Both structures reveal a heterotrimeric complex containing two SH3 domains held together by a single peptide. Trimerization also occurs in solution and is facilitated by the pseudo-symmetrical peptide sequence. Moreover, ternary complexes of CIN85 and Cbl are formed in vivo and are important for the ability of Cbl to promote epidermal growth factor receptor (EGFR) downregulation. These results provide molecular explanations for a novel mechanism by which Cbl controls receptor downregulation. |
==About this Structure== | ==About this Structure== | ||
| - | 2AK5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http:// | + | 2AK5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AK5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bravo, J.]] | [[Category: Bravo, J.]] | ||
[[Category: Cardenes, N.]] | [[Category: Cardenes, N.]] | ||
| - | [[Category: Deribe, Y | + | [[Category: Deribe, Y L.]] |
[[Category: Dikic, I.]] | [[Category: Dikic, I.]] | ||
[[Category: Groemping, Y.]] | [[Category: Groemping, Y.]] | ||
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[[Category: x-ray]] | [[Category: x-ray]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:28:18 2008'' |
Revision as of 14:28, 21 February 2008
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beta PIX-SH3 complexed with a Cbl-b peptide
Overview
The ubiquitin ligases c-Cbl and Cbl-b play a crucial role in receptor downregulation by mediating multiple monoubiquitination of receptors and promoting their sorting for lysosomal degradation. Their function is modulated through interactions with regulatory proteins including CIN85 and PIX, which recognize a proline-arginine motif in Cbl and thus promote or inhibit receptor endocytosis. We report the structures of SH3 domains of CIN85 and beta-PIX in complex with a proline-arginine peptide from Cbl-b. Both structures reveal a heterotrimeric complex containing two SH3 domains held together by a single peptide. Trimerization also occurs in solution and is facilitated by the pseudo-symmetrical peptide sequence. Moreover, ternary complexes of CIN85 and Cbl are formed in vivo and are important for the ability of Cbl to promote epidermal growth factor receptor (EGFR) downregulation. These results provide molecular explanations for a novel mechanism by which Cbl controls receptor downregulation.
About this Structure
2AK5 is a Protein complex structure of sequences from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Cbl promotes clustering of endocytic adaptor proteins., Jozic D, Cardenes N, Deribe YL, Moncalian G, Hoeller D, Groemping Y, Dikic I, Rittinger K, Bravo J, Nat Struct Mol Biol. 2005 Nov;12(11):972-9. PMID:16228008
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