2ak5
From Proteopedia
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'''beta PIX-SH3 complexed with a Cbl-b peptide''' | '''beta PIX-SH3 complexed with a Cbl-b peptide''' | ||
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[[Category: Moncalian, G.]] | [[Category: Moncalian, G.]] | ||
[[Category: Rittinger, K.]] | [[Category: Rittinger, K.]] | ||
| - | [[Category: | + | [[Category: Adaptor protein]] |
| - | [[Category: | + | [[Category: Cbl]] |
| - | [[Category: | + | [[Category: Cin85]] |
| - | [[Category: | + | [[Category: Endocytosis]] |
| - | [[Category: | + | [[Category: Pix/cool]] |
| - | [[Category: | + | [[Category: Protein-protein interaction]] |
| - | [[Category: | + | [[Category: X-ray]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:09:05 2008'' | |
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Revision as of 16:09, 3 May 2008
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 Page seeded by OCA on Sat May 3 19:09:05 2008
